Planst and Their Effect Antitumor

Nutrition and Cancer
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/hnuc20
RENISUS Plants and Their Potential Antitumor

Effects in Clinical Trials and Registered Patents
Diorge Jônatas Marmitt , Shanna Bitencourt , Gustavo Rodrigo da Silva ,

Claudete Rempel & Márcia Inês Goettert
To cite this article: Diorge Jônatas Marmitt , Shanna Bitencourt , Gustavo Rodrigo da
Silva , Claudete Rempel & Márcia Inês Goettert (2020): RENISUS Plants and Their Potential
Antitumor Effects in Clinical Trials and Registered Patents, Nutrition and Cancer, DOI:
10.1080/01635581.2020.1810290
To link to this article: https://doi.org/10.1080/01635581.2020.1810290
Published online: 24 Aug 2020.
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NUTRITION AND CANCER
https://doi.org/10.1080/01635581.2020.1810290
REVIEW
RENISUS Plants and Their Potential Antitumor Effects in Clinical

Trials and Registered Patents
^natas Marmitta , Shanna Bitencourta
Diorge Jo , Gustavo Rodrigo da Silvab , Claudete Rempelc ,
and Marcia Ine^s Goetterta
a
Laboratorio de Cultura de Celulas, Programa de Pos-graduaç~ao em Biotecnologia, Universidade do Vale do Taquari (Univates),
Lajeado, Brazil; bCentro de Ciências Biologicas e da Saude, Universidade do Vale do Taquari (Univates), Lajeado, Brazil; cPrograma de
Pos-graduaç~ao em Ambiente e Desenvolvimento/Programa de Pos-graduaç~ao em Sistemas Ambientais Sustentaveis, Universidade do
Vale do Taquari (Univates), Lajeado, Brazil
ABSTRACT ARTICLE HISTORY

Cancer is a significant cause of morbidity and mortality. Scientific advances, coupled with Received 27 December 2019
potential flaws in current treatments, are driving research into the discovery of new bio- Accepted 9 August 2020
active molecules. This systematic review focused on scientific studies with clinical trials and
patents registered on the National Relation of Medicinal Plants of Interest to the Unified
Health System (RENISUS) plants (or derivative compounds) with antitumor potential. Studies
with 19 different forms of cancer were found, the prostate being the organ with the highest
research incidence and the species Glycine max, Curcuma longa, and Zingiber officinale,
beside the phytochemicals curcumin and soy isoflavone were the most tested in clinical
trials/patents.
Introduction dramatically with age; the overall risk combines with

the tendency for cellular repair mechanisms to be less
Cancer is the second leading cause of death globally,
about 1 in every 6, and it was responsible for an esti- effective as a person grows older (5). In this context,
mated 9.6 million deaths in 2019. From this index, the economic impact of cancer is significant and
approximately 70% of deaths from cancer occur in increasing. The total annual financial cost of cancer in
low and middle-income countries, like Brazil (1). 2010 was estimated at approximately US$1.16 tril-
Around one-third of deaths from cancer are due to lion (6).
the following behavioral and dietary risks: high body A correct cancer diagnosis is essential for adequate
mass index, low fruit and vegetable intake, lack of and effective treatment because every cancer type
physical activity, alcohol use and tobacco smoking (2). requires a specific treatment regimen that encom-
Tobacco smoking is the most crucial risk factor for passes one or more modalities such as surgery, radio-
cancer development, and it is responsible for approxi- therapy, and chemotherapy aiming for cancer
mately 22% of cancer deaths (3), being lung the most remission (7). Therefore, the recognition of the wide-
prevalent cancer (2.09 million cases), and with the spread applicability of these concepts will increasingly
highest number of fatalities (1.76 million). In Brazil, affect the development of new means to treat human
prostate cancer is the most pervasive, with an esti- cancer (8). Over the last few decades, new adjuvant
mated 68,220 new prostate cancer cases for each year therapies that improve therapeutic outcomes for some
of the 2018–2019 biennium. These values correspond types of cancer have sought to combine chemotherapy
to an estimated risk of 66.12 new cases per 100,000 with different mechanisms of action, such as radiation
men. Breast cancer follows with approximately 59,700 therapy, and the use of targeted therapies. However,
new cases for each year of the 2018–2019 biennium, a there are still many flaws in these treatment
calculated risk of 56.33 cases per 100,000 women (4). responses (9).
Aging is another fundamental factor in the devel- In this sense, the research for new molecules
opment of cancer. The incidence of cancer rises focuses on natural products that show enormous
CONTACT Diorge Jônatas Marmitt [email protected] Laborat

orio de Cultura de Celulas, Programa de P
os-graduaç~ao em Biotecnologia,
Universidade do Vale do Taquari (Univates) Avelino Talini street, 171, 95914-014, Lajeado, RS, Brazil.
ß 2020 Taylor & Francis Group, LLC
2 D. J. MARMITT ET AL.
potential for generating anticancer agents, presenting electronic databases. MEDLINE/PubMed is one of the
pharmacological and molecular characteristics that most important international databases, with over 28
favor such development (10). Great results from plant million citations for biomedical and life sciences
research, responsible for the development of chemo- literature. Consequently, after a quick advanced search
therapeutic drugs such as paclitaxel (TaxolV) and on this portal using the terms ‘cancer’ and ‘plants,’
R
docetaxel (TaxotereV), approved in the 1990s and

R
39,970 items were listed. After filtering the search and
used in breast cancer treatment; as vincristine adding the terms ‘In Vitro’ and ‘In Vivo’ as the
(OncovinV) and vinblastine (VelbanV), both from the
R R
keywords, 11,188 results were found. To contribute to
’60s and still effectively used in the treatment of the dissemination of recognized scientific value
various types of cancer; indicate a promising path and publications, we chose to divide the selection and
stimulate the constant search for new natural products analysis of studies of interest into three stages: the
capable of correcting flaws that have occurred in first quantitative and two last qualitative ones.
conventional treatments (11).
In parallel, the Brazilian Ministry of Health
Stages of Study
published in February 2009 the National Relation of
Medicinal Plants of Interest to the Unified Health Given the high volume of scientific research on cancer
System (RENISUS), to encourage the use of comple- and plants, the initial stage aimed just to show the
mentary therapies with plants in the Brazilian Unified number of preclinical scientific studies with the
Health System (SUS). It appears in the list, 71 plant RENISUS plants associated with anticancer effects
species, many of them native to Brazil, however, indexed in the MEDLINE/PubMed portal.
most are exotic species, plants easily grown and used Still, it was necessary to refine the search, concen-
in other countries, often in the form of food or spices, trating on more advanced studies with RENISUS
such as garlic, saffron, soybeans and ginger, for plants. In that way, in the second step, publications
example (12). It is also worth noting that the public indexed in two electronic databases were selected.
health system in Brazil offers herbal medicines derived In addition to the MEDLINE/PubMed database,
from plants from the RENISUS. The National the second stage of the research evaluated the
Relation of Essential Medicines (RENAME) establishes ClinicalTrials.gov portal, a database of human patient
the list of 12 free herbal medicines available in SUS clinical trial records conducted worldwide by public
(13). In order to guide and encourage professionals and private institutions; it publishes information on
to prescribe herbal medicines, the Brazilian Health medical studies in human volunteer patients. These
Regulatory Agency (ANVISA) has published the clinical trials submit volunteers to medical interven-
Phytotherapeutic Memento, which gathers informa- tions and observe its safety and efficacy. All proce-
tion on the therapeutic use and botanical characteris- dures are filed and obey US medical laws (22).
tics of medicinal plants (14). New compounds are developed, and to guarantee
Several RENISUS plants have already been eval- the use of these discoveries, the registration of the
uated for their therapeutic effects, or even as coadju- intellectual property is necessary, which regulates the
vants for different pathologies (12,15–18). However, acquisition, use, and exercise of rights and interests
although several studies have demonstrated the poten- over the differentiation of intangible assets susceptible
tial of RENISUS plants to mitigate the effects of che- to commercial use. In this sense, the third and final
moprevention (19–21), a summary of information step of the research evaluated patents registered and
about their impact on Human Clinical Trials and reg- available for consultation at the European Patent
istered patents is not available. Thus, this study aimed Office (EPO) and WIPO Patentscope involving
to present a systematic review of the literature on the RENISUS plants and their antitumor effects.
anticarcinogenic effects of the medicinal plants present
in the RENISUS. Search Strategy
As a research strategy to carry out this systematic
review, two reviewers were responsible for the
Methods
searches of publications and patent registrations
This systematic review focused on scientific studies potentially relevant about RENISUS plants (or deriva-
and registered patents about RENISUS plants (or tive compounds) associated with anticarcinogenic
derivative compounds) with antitumor potential. The effects. All full and open access texts published until
publications of interest are indexed in two renowned September 2018 were considered in all stages of the
NUTRITION AND CANCER 3
Figure 1. PRISMA flow diagram of the literature search and study selection process.
search, regardless of language. The International Plant EPO website, an ‘Advanced search’ was conducted, in
Name Index was used to verify the names of species. the ‘Title or abstract’ field, the scientific name of the
The Guideline of the Preferred Reporting Items for plants of RENISUS and the words ‘cancer’, ‘malignant
Systematic Reviews and Meta-Analyses (PRISMA) was tumor’, ‘carcinoma’, and ‘neoplasms’ were inserted.
used for designing this systematic review (Figure 1). Patents indexed in the WIPO Patentscope system
To do so, in the first step the terms used in the were also consulted and analyzed. Using the simple
consultation were the scientific names of the 71 medi- search tab, the same terms entered in the EPO search
cinal plants listed in RENISUS, besides descriptors were examined. From initial search, as an inclusion
associated with the search focus: ‘cancer,’ ‘malignant criterion, the reviewers evaluated each patent’s
tumor,’ ‘carcinoma,’ ‘neoplasia,’ ‘In Vitro,’ and abstract individually to select those that already indi-
‘In Vivo.’ In the second stage of the evaluation, in the cated tests in humans.
MEDLINE/PubMed database, the keywords used to
search were again the scientific names of the 71 medi-
cinal plants as described in RENISUS, and the terms Inclusion and Exclusion Criteria
‘cancer,’ ‘malignant tumor,’ ‘carcinoma,’ ‘neoplasms,’ In order to be considered in this analysis, studies had
besides ‘clinical trials.’ In the ClinicalTrials.gov portal, to meet the following criteria: antitumoral effects of
to refine the search to more specific results, we opted the medicinal plant (steps one and two); therapeutic
for the advanced search using the filters: Condition or evidence in clinical trials (step two); patents on meth-
disease (cancer; carcinoma; malignant neoplasm; ods or formulations with RENISUS plants (or deriva-
tumor; neoplasia); Other terms (scientific names of tive compounds) available for consultation (step
the 71 medicinal plants listed in RENISUS); Study three). Any kind of reviews, semi-structured inter-
Results (Study With Results); Status: Recruitment views, letters, commentaries, and guideline articles
(Active, not recruiting; Terminated; Completed). were not computed. Conference abstracts and studies
In the third and final stage, the EPO database was that only mentioned the empirical use of the plants
consulted, the leading European patent body. On the were also disregarded.
Research eligibility was performed in pairs; two studied form of cancer In Vitro among MEDLINE/
reviewers were responsible for independently analyz- PubMed publications, and the major cell lines tested
ing the studies and patents selected. The data analysis in the studies were A549 (26), H1975 (45), and LL/
and interpretation were guided by fundamental items 2 (25).
that led to the method description, which was detailed The mechanisms of action suggested in these stud-
in tables: structure/amount of the plant and phytocon- ies generally demonstrate antiproliferative (27,46),
stituents used, clinical outcomes (variables studied, pro-apoptotic (27–34), anti-metastatic (47,48), and
main results, and possible mechanisms of action). antiangiogenic (25,33) effects from various phyto-
chemicals/plants In Vitro and In Vivo. Cancer is one
of the scenarios in which little apoptosis occurs,
Results and Discussion
resulting in malignant cells that do not die, leading to
The recent update by Newman & Cragg reports that, tumor metastasis and resistance to anticancer drugs.
from the total number of new chemical entities Apoptosis plays a vital role in cancer treatment
released between 1981 and 2019 (1,881), 53% are because it is a popular target of many treatment strat-
either a natural product or derived from one. egies (49). In the In Vitro/In Vivo studies found, 337
Regarding molecules directed to cancer treatment, the results directly address the induction of apoptosis
247 molecules (compounds) developed in this period, involved in the antitumor mechanism (27–29,31,34).
75% come from natural products and their derivatives. Currently, anticancer therapies in clinical use are cyto-
The work also indicates that more than 60% of the toxic, and when they work, induce apoptosis of malig-
antitumor compounds used in medicine were devel- nant cells. Cytotoxic chemotherapy and antiangiogenic
oped based on natural products and their deriva- therapy are each dependent on endothelial cell apop-
tives (23). tosis (50). Tumor angiogenesis is a crucial point of
Within PubMed’s database, more than three mil- control for cancer progression, so the inhibition of
lion publications correspond to cancer; the proportion angiogenesis seeks to limit the tumor’s ability to grow
has significantly increased from around 6% in 1950 to and metastasize. Although not fully understood, the
16% in 2016. None of the other conditions are close complex process of tumor angiogenesis involves the
to cancer in the number of studies in PubMed. Even highly regulated orchestration of multiple signaling
the more general term ‘Infection’ was more than 10% pathways. In this context, 246 In Vitro/In Vivo studies
below cancer in 2016 (24). The literature has a consid- described the antiangiogenic effect of the compounds
erable amount of reports about cancer. In this evalu- or extracts (25,33,51). Studies have focused on the
ation, using as search terms the scientific names of vascular endothelial growth factor (VEGF) pathway
the 71 medicinal plants listed in RENISUS, associated (33,51), which plays a central role in angiogenesis and
with ‘cancer,’ ‘malignant tumor,’ ‘carcinoma,’ is often highly expressed in various forms of can-
‘neoplasia,’ and ‘In Vitro,’ 1,716 registers in cer (52).
MEDLINE/PubMed were found. There were 210 Because of the high volume of scientific research
results with the Curcuma longa L. plant (25,26), fol- on cancer and plants, it was necessary to refine the
lowed by Allium sativum L. (175 articles) (27,28), search, prioritizing and concentrating on more
Glycine max (L.) Merr. (167 studies) (29,30), and advanced studies with RENISUS plants. Thus, in the
Zingiber officinale Roscoe (88 searches) (31,32). When next step, selected publications were indexed in two
replacing the term ‘In Vitro’ by ‘In Vivo,’ the search electronic databases about clinical trials. Table 1
found 931 results, and again, the most cited plants shows the main details of human studies involving
were C. longa with 135 searches (33,34), followed by RENISUS plants (or derivative compounds) published
A. sativum with 115 studies (35,36), G. max with 95 in MEDLINE/PubMed.
articles (37,38), and Z. officinale with 44 searches Analyzing the data in Table 1, we can observe that
(39,40). About these results, studies targeting breast among the 71 plants on the RENISUS list, 19 plant
tumors treatment, followed by lung tumors, have con- species feature in clinical researches in humans. Of
centrated the most significant amount of publications. these, the species Phyllanthus urinaria L. and U.
Studies aiming In Vitro breast tumors treatment took tomentosa are native plants from Brazil. In the SUS,
place with five distinct lines (MCF-7 (30), EMT6 (41), the phytotherapeutic species A. vera, C. scolymus, G.
MDA-MB-2314 (42), MDA-MB-435S (43) and T47D max, M. piperita, and U. tomentosa are distributed
(44)), and a large part of these studies contemplated free of charge. Three plants concentrate approximately
C. longa. Lung tumors appear as the second most 49% of the studies selected in Table 1, G. max, 14
Table 1. Overview of the investigated plants, their main results in randomized controlled human trials published in
MEDLINE/PubMed.
Part of the plant/compound/
Plant species (Family) Concentration Summary of intervention Type of study
Achillea millefolium L. A. millefolium distillate was prepared The experimental group of 56 patients with Randomized, controlled trial
(Asteraceae) with 10 kg of yarrow plant flower chemotherapy-induced Oral Mucositis (IRCT2013092214729N1) (53)
and 50 L of water (OM) gargled 15 mL of a mixture of
routine solution or distilled A. millefolium
4 times a day for 14 days. A. millefolium
distillate healed OM much more than the
routine solution
Allium sativum L. A garlic-containing meal (100 g white 17 volunteers consumed a garlic-containing Randomized, crossover trial
(Amaryllidaceae) bread, 15 g butter, and 5 g raw meal after 10 days of consuming a (NCT01293591) (54)
crushed garlic) controlled, garlic-free diet. The oncostatin
M is a pleiotropic cytokine that inhibits
several tumor cell lines in culture and
was significantly higher than in the
control group
A. sativum Garlic tablets with doses of 900 mg a 95 Patients receiving chemotherapy for Placebo-controlled, double-
day, divided into 2 doses of 450 mg hematological malignancies are at high blind, randomized study
active compound (allin 9,9 mg, risk for Febrile Neutropenia (FN). Those (NCT00247039) (55)
allicin 4,5 mg) patients receiving garlic tablets
developed fewer FN episodes, especially
those with severe neutropenia. Garlic
appeared to exert a protective effect in
the lower-risk subgroup
A. sativum Garlic supplement containing 400 mg 7.3 years of oral supplementation with Intervention trial
of Aged garlic extract (AGE) garlic extract and oil (n ¼ 1,678) were (NCT00339768) (56)
(Wakunaga Pharmaceutical Co.) and associated with non-statistically
2 mg of steam-distilled garlic oil, significant reductions in gastric cancer
given twice daily incidence and mortality
A. sativum Garlic supplement containing 1 g The effects of a 7.3 years supplementation Randomized, double-blind,
twice daily (Wakunaga with garlic increased the serum folate placebo-controlled, factorial
Pharmaceutical Co.) and 2 mg of concentration, and the vitamin and trial (NCI-OH-95-C-N029) (57)
steam-distilled garlic oil, given selenium supplement increased that of
twice daily glutathione, retarding the development
of precancerous gastric lesions in
3,411 subjects
A. sativum Not informed Diets rich in fruit and garlic are modestly Prostate, lung, colorectal, and
associated with reduced risk of colorectal ovarian cancer screening
adenoma in 3,057 cases observed with at trial (58)
least one prevalent histologically verified
adenoma of the distal large bowel, with
29,413 control subjects
A. sativum High-dose AGE (2,4 mL/d) as an active In 51 patients with colorectal adenomas, Preliminary double-blind,
treatment and low-dose AGE the number of adenomas increased randomized clinical trial (59)
(0,16 mL/d) as a control linearly in the control group, but AGE
significantly suppressed both the size
and number of colon adenomas in
patients after 12 months of high-
dose treatment
A. sativum The daily dose (4 capsules, Wakunaga AGE was administered for 6 months in 42 Randomized, double-blind
Pharmaceutical Co.), contained patients with liver cancer (84%), 7 trial (60)
500 mg of AGE, 727 mg of patients with pancreatic cancer (14%),
crystalline cellulose, and 11 mg of and 1 patient with colon cancer (2%)
sucrose fatty acid ester and the study showed that administering
AGE to patients with advanced cancer of
digestive system improved Natural Killer
cells (NK cells) activity
A. sativum Dietary supplement “Karinat” (beta- 33 patients were given a tablet of karinat Randomized, double-blind,
carotene 2,5 mg, alpha-tocopherol twice a day for 6 months. It was found placebo-controlled trial (61)
5 mg, ascorbic acid 30 mg, and that karinat reduced the severity of
garlic powder 150 mg per tablet) mastalgia, dysmenorrhea, and
algomenorrhea, and caused the
regression of palpable symptoms of the
breast fibromatosis. On the whole,
karinat had positive action in 75.8%
of patients
A. sativum 200 mg synthetic allitridum compound In 2,526 participants aged 35–74 years, the Double-blind intervention
every other day for one month of morbidity rates of malignant tumors in study (62)
each year from November 1989 to the intervention group declined by 22%,
December 1991 and the compound may effectively
prevent gastric cancer, especially in men
Aloe vera L. (Asphodelaceae) A. vera 3% ointment, 1 g twice a day In 20 patients with Acute Radiation Proctitis Double-blind, placebo-controlled
for 4 weeks after radiation therapy in pelvic trial (63)
(Continued)
Table 1. Continued.
malignancies, there was a significant
improvement in the symptom index
(before treatment vs. after treatment
with A. vera) for diarrhea, fecal urgency,
total clinical presentation, Radiation
Therapy Oncology Group total
and lifestyle
A. vera A. vera mouthwash containing pure A. Twenty-six Head and Neck Cancer (HNC) Triple-blind, randomized
vera gel (Barij A. vera sirup, Barij patients received an A. vera mouthwash controlled trial (64)
Essence Pharmaceutical Co; Iran) that was beneficial in alleviating the (IRCT2012072410377N1)
severity of radiation-induced mucositis
and showed no side effects in patients
with HNCs
A. vera and Curcuma longa L. Basant polyherbal vaginal cream A total of 280 women with Human Phase II randomized controlled
(Zingiberaceae) (containing extracts of curcumin, Papillomavirus (HPV) infection were study (65)
reetha, amla, and A. vera) (5 ml per instructed to use one application of the
application) and curcumin soft formulation daily for 30 consecutive days,
gelatin vaginal capsules (500 mg except during menstruation. The HPV
curcumin per capsule) clearance rate in the Basant arm (87.7%)
was significantly higher than the
placebo. Curcumin capsules caused a
higher rate of clearance (81.3%) than
the placebo
A. vera A commercially available lotion The prophylactic use of A. vera reduced the Self-controlled clinical trial (66)
containing A. vera in addition to intensity of radiation-induced dermatitis
lanolin oil, glyceryl stearate, diluted in the trial with 60 patients who had
collagen, tocopherol, allantoin, breast cancer (38%), followed by pelvic
and paraben (32%), head-and-neck (22%) and other
cancers (8%), and were asked to use the
lotion on one half of the irradiated area
twice a day from the beginning of
treatment until 2 weeks after the end of
radiotherapy
A. vera Metal Esculetina plus Ginko Biloba and A group of 20 patients affected by breast Randomized controlled
A. vera (Radioskin 2VR) cancer used the topical treatment study (67)
Radioskin 2 that was applied twice a day,
starting 15 days before and ending one
month after treatment with radiations
and confirmed the protective role of the
effective cream, and showed its efficiency
to identify radiation-induced dermatitis
at a very early stage
A. vera A. vera solution consisted of 94.5% 58 patients with HNC gurgled and ingested Phase II double-blind,
aloe juice, 5% pear juice 20 mL of A. vera solution four times a randomized study (68)
concentrate, 0.4% lemon-lime day, starting on the first day and
flavor, and 0.1% citric acid continuing through the radiotherapy
course. The mean Quality of Life (QoL)
scores were higher in the A. vera group
than in the control one
A. vera Mild soap and A. vera gel Mild soap and A. vera gel would decrease Prospective, randomized,
the incidence of skin reactions in blinded clinical trial (69)
patients undergoing radiation therapy
when the cumulative dose increases
over time
A. vera A. vera tincture (A. vera leaves: 10%; 50 patients who have lung cancer, Clinical study (70)
40 alcohol: 90%) (1 ml twice/day) gastrointestinal tract tumors, breast
cancer, or brain glioblastoma were
treated with Pineal Indole Melatonin
(MLT) plus A. vera tincture, a partial
response was achieved in 2/24 patients
treated, and stable disease was achieved
in 12/24 patients treated. Therapy with
MLT plus A. vera extract may produce
some therapeutic benefits in terms of
stabilizing disease and survival in
patients with advanced solid tumors
Bidens pilosa L. (Asteraceae) FITOPROT A – (mucoadhesive Patients rinsing their mouths with FITOPROT Phase I double-blind,
formulation containing 10 or A three times a day, for ten consecutive randomized study (71)
20 mg/mL of curcuminoids extract days demonstrated it to be safe and
plus 20 or 40% v/v of B. tolerable, and it is suitable for evaluation
pilosa extract) in a phase II trial as a treatment against
chemoradiotherapy-induced OM in
patients with HNC
(Continued)
Table 1. Continued.
Calendula officinalis C. officinalis oil lotion (4% Calendula In the 51 patients with HNC in radiotherapy Randomized, double-blind,
L. (Asteraceae) oil) applied topically every 12 hours treatment with Calendula lotion showed controlled clinical trial
(twice/day), from the first to the better therapeutic response than the (Brazilian Registry of Clinical
last day of radiotherapy session essential fatty acids group in the Trials: RBR-237v4b) (72)
prevention and treatment of
radiodermatitis
C. officinalis Calendula ointment (calendula extract In 126 breast cancer patients who had Phase III randomized trial (73)
ointment; Boiron Ltd, France). The undergone surgery and received
digest is obtained by incubation at ointment in the irradiated areas after
75 C in petroleum jelly to extract each session, the occurrence of grade 2
the liposoluble components of or higher acute dermatitis was
the plant significantly lower (41% to 63%) with the
use of marigold ointment. Marigold
should be proposed for patients
submitted to postoperative irradiation for
breast cancer
Matricaria chamomilla L. Flowers and aerial parts of M. recutita Sixty patients undergoing Hematopoietic Randomized, double-blind,
(Asteraceae) and Mentha and peppermint oil were used for Stem Cell Transplantation (HSCT) placebo-controlled clinical
piperita L. (Lamiaceae) mouthwash preparation based on a received the mouthwash one week trial (74)
formulation of 1% v/v peppermint before HSCT and were instructed to use
oil, 1% w/v dried extract of M. it three times a day for at least 30 days.
recutita and 99% v/v ethanol 96 The duration, maximum and average
daily grade of OM were significantly
reduced in the treatment group, which
led to significant improvements in pain
intensity and reduced the need for
complementary medications
M. chamomilla 500 mg capsules of powdered ginger In 65 women undergoing chemotherapy for Randomized, double-blind
root, and 500 mg capsules of M. breast cancer, the group that applied clinical trial (75)
chamomilla extract (two times a ginger and chamomile for 5 days before
day) in addition to a routine and 5 days after chemotherapy showed
antiemetic regimen consisting of it was significantly effective in reducing
dexamethasone, metoclopramide, the frequency of vomiting and may
and aprepitant capsules relieve Chemotherapy-Induced Nausea
and Vomiting (CINV)
M. chamomilla Mouthwash containing M. chamomilla In 40 patients undergoing HSCT, the 1% Randomized, controlled, phase II
dosages of 0.5%, 1%, or 2% w/w dosage mouthwash group demonstrated clinical trial (76)
liquid extract reduced incidence, intensity, and
duration of OM, compared with the
control group
C. longa Indian turmeric powder with honey In 30 cancer patients undergoing Randomized, double-blind
chemotherapy and radiotherapy with placebo (77)
treatment-induced OM, it is inferred that
the application of Indian turmeric and
honey on OM is effective in its reduction
C. longa ViccoVR Turmeric Cream (VTC) 2 g; In 50 patients with HNC undergoing Cohorts pilot study (78)
Vicco Laboratories, India, a turmeric radiotherapy, prophylactic application of
and sandalwood oil (Santalum the cream was initiated on day 1 and
album L.) based cream continued every day until 2 weeks after
the end of treatment (five times a day
(2 h before, immediately after, 2 h after
and 4 and 6 h after radiotherapy). The
occurrence of grade 3 dermatitis was
lower in the cohorts using VTC, that
showed to be effective in preventing
radiodermatitis
C. longa Bioavailability-boosted curcuminoids In 80 subjects with solid tumors and under Randomized, double-blind,
preparation (180 mg/day; n ¼ 40) standard chemotherapy regimens, placebo-controlled trial (79)
for a period of 8 weeks curcuminoid supplementation was
associated with a significant
improvement in health related QoL and
suppression of the systemic inflammation
C. longa and Punica granatum A tablet containing among others: A total of 199 men with localized prostate Double-blind, placebo-controlled
L. (Lythraceae) turmeric powder (C. longa) 100 mg, cancer, average age 74 years, 60% randomized trial (80)
pomegranate whole fruit powder managed by Primary Active Surveillance
(P. granatum) 100 mg, taken three (AS), and 40% by watchful waiting. A
times a day for 6 months significant short-term, favorable effect on
the percentage rise in serum Prostate
Specific Antigen (PSA) was found in men
managed by AS and watchful waiting
(Continued)
Table 1. Continued.
following ingestion of this well-tolerated,
specific blend of concentrated foods
C. longa Turmeric solutions powder (Himalaya The patient was instructed to gargle with Single-blind, randomized,
Drug Company, India) (curcumin 10 mL of the turmeric solution for about clinical trial (81)
2,42% w/w) one turmeric capsule 2 minutes and expectorate, repeating 4
(400 mg) in approximately 80 mL of times at each time point for a total of 6
boiled and cooled water times in a day (1 hour prior to radiation,
1, 2, 4, and 6 hours after radiation, and
once before going to bed). In 40 HNC
patients undergoing radiation therapy, it
provided significant benefit, delayed and
reduced the levels of radiation-induced
OM, and decreased intolerable mucositis
C. longa Turmeric powder 5 g 3 times/day In 50 patients with chronic myeloid Prospective, descriptive pilot
(dissolved in 150 mL of milk to leukemia, the nitric oxide levels study (82)
improve its palatability and significantly decreased in the group
absorption) for 6 weeks receiving the turmeric. Turmeric acts as
an adjuvant to imatinib in decreasing the
nitric oxide levels and may help in the
treatment of chronic myeloid
leukemia patients
C. longa Curcumin was orally given from In 14 patients with advanced or metastatic Phase I dose escalation trial (83)
500 mg/day for seven consecutive breast cancer, the recommended dose of
days by cycle and escalated until a curcumin was 6 g/day for seven
dose-limiting toxicity should occur consecutive days every 3 weeks in
combination with a standard dose
of docetaxel
C. longa and Cynara scolymus Combination botanical supplement In 40 healthy premenopausal women, over Placebo-controlled, parallel-arm,
L. (Asteraceae) including C. longa and C. scolymus, five menstrual cycles, during the early pilot (84)
dietary changes (3 servings/day follicular phase, the botanical
dark leafy greens, 30 g/day fiber) supplement decreased
dehydroepiandrosterone,
dehydroepiandrosterone-sulfate,
androstenedione and estrone-sulfate.
Early-follicular phase androgens
decreased with the botanical
supplement, recommended for breast
cancer prevention
C. longa Gelatin capsules containing 0.2 mL of Turmeric demonstrated potential for Phase I clinical trial (85)
turmeric oil reversing oral submucous fibrosis, a
precancerous condition for oral cancer,
and can be recommended directly for a
Phase II trial in patients
C. longa Starting dose was 500 mg/day and Curcumin was not toxic to humans up to Phase I clinical trial (86)
escalated to another level in the 8 g/day when taken by mouth for 3
order of 1, 2, 4, 8, and 12 g/day, months. Our results in 25 patients also
and was taken orally for 3 months suggest a biologic effect of curcumin in
the chemoprevention of recently
resected urinary bladder cancer, uterine
cervical intraepithelial neoplasm, oral
leucoplakia and intestinal metaplasia of
the stomach
C. longa Curcuma extract in capsules at doses Ingestion of 440 mg of Curcuma extract for Dose-escalation pilot (87)
between 440 and 2,200 mg/day, 29 days was accompanied by a 59%
containing 36–180 mg of curcumin, decrease in lymphocytic glutathione S-
taken daily for up to 4 months transferase activity in fifteen patients
with advanced colorectal cancer
refractory to standard chemotherapies.
The results suggest that the extract can
be safely administered to patients at
doses of up to 2.2 g daily, equivalent to
180 mg of curcumin
Glycine max L. Merrill The tomato-plus intervention included, Three-week nutritional interventions with Randomized controlled trial
(Fabaceae) and among others, pomegranate and tomato-products combined with (NCT00433797) (88)
P. granatum grape juice (330 mL of each), and selenium and fatty acids lowered PSA
200 mg soy isoflavones per day levels in 79 patients with non-metastatic
prostate cancer
G. max Two slices of soy bread (34 mg In 32 patients with prostate cancer with Randomized, phase II trial (89)
isoflavones/slice) or soy bread asymptomatic biochemical recurrence but
containing almond powder daily as no measurable disease on standard
a source of b-glucosidase for staging studies, soy bread modulates
56 days systemic soluble and cellular biomarkers
(Continued)
Table 1. Continued.
consistent with limiting inflammation
and inhibiting myeloid-derived
suppressor cells
G. max Soy bread and soy-almond bread with Findings from this study with 32 men with Randomized, phase II, crossover
60 mg aglycone equivalents of asymptomatic prostate cancer provide trial (90)
isoflavones per day for 8 weeks the necessary framework to study
isoflavone-metabolizing phenotypes as a
strategy for identification of individuals
that might benefit or show resistance to
cancer preventive strategies using
dietary soy
G. max Fermented Soybean Extract (MicrSoy- In 143 patients undergoing chemotherapy, Randomized, cross-over,
20) (MicroBio Co., Taiwan) was the addition of MicrSoy-20 for 8 weeks comparative trial (91)
administered orally, in fasting as an adjuvant to chemotherapy can be
conditions, at a dose of 5 mL every effective in improving QoL for
morning and 3 mL every afternoon, cancer patients
diluted in 100 mL of warm water
G. max and C. longa Botanical preparation (MB-6) - 72 patients with metastatic colorectal Two-arm, multicenter, double-
MicroBio Co., Taiwan - composed, cancer were treated with MB-6, the blind, randomized, placebo-
among others, of MicrSoy-20, and dosage included 6 capsules of 320 mg controlled clinical (92)
curcumin (C. longa) each administered 3 times daily with
meals. The primary outcome was the
best overall response, and secondary
outcomes included progression-free
survival, overall survival. Patients in the
MB-6 group had a significantly lower
disease progression rate than patients in
the placebo group
G. max Soy isoflavone capsules (80 mg/day of In 42 men with localized prostate cancer Double-blind, randomized,
total isoflavones) for up to six treated with soy, 12 genes involved in placebo-controlled trial
weeks prior to scheduled cell cycle control and 9 genes involved in (NCT00255125) (93)
prostatectomy apoptosis were down regulated in the
treatment of tumor tissues versus the
control group
G. max Soy compound genistein (300 or In 59 subjects diagnosed with urothelial Phase II, randomized, placebo-
600 mg/day as the purified soy bladder cancer, genistein phytoestrogen controlled trial (94)
extract G-2535) administered for 14 displayed a possible bimodal effect
to 21 days before surgery (more effective at the lower dose) on
bladder cancer tissue Epidermal Growth
Factor Receptor (EGFR) phosphorylation.
Genistein has induced a significant
reduction in the EGFR phosphorylation
G. max 30 mg synthetic genistein In 23 patients with localized prostate Placebo-controlled, block-
administered daily for 3 to 6 weeks cancer, PSA levels decreased by 7.8%, randomized, double-blind
prior to prostatectomy and total cholesterol was significantly Phase II (95)
lower in the genistein arm. Plasma
concentrations of total genistein were on
average 100-fold higher in the genistein
arm after treatment
G. max 200 mg soy isoflavone daily for 6 In 42 patients with prostate cancer, the Pilot study (96)
months beginning in the first day symptoms in soy-treated patients were
of radiation therapy further improved after 6 months,
compared to the placebo group. Soy
isoflavones taken in conjunction with
radiation therapy could reduce the
urinary, intestinal, and sexual adverse
effects in patients with prostate cancer
G. max Soy supplements (82 mg/day aglycone In 19 men with prostate cancer who had Double-blind, randomized,
equivalents) for 2 weeks prior elected to undergo radical placebo-controlled trial (97)
to surgery prostatectomy, the prostate tissue
demonstrated having the ability to
concentrate dietary soy isoflavones to
potentially anticarcinogenic levels. Total
isoflavone concentrations were an
average of approximately 6-fold higher in
prostate tissue compared to serum
G. max A capsule containing 40 mg of a soy The 22 of 33 (67%) evaluable patients with Phase II clinical trial (98)
isoflavone composition twice a day prostate cancer in the lycopene plus soy
orally for a maximum of 6 months isoflavone group achieved stable disease
level described as stabilization in serum
(Continued)
Table 1. Continued.
PSA level. Soy isoflavones may delay
progression of both hormone-refractory
and hormone-sensitive cancer
G. max 60 mg/per day of soy isoflavones for a In 59 patients with early stage prostate Double-blind, randomized,
12-week period cancer supplemented with soy placebo-controlled trial (99)
isoflavones, even in a short duration
study, a change in surrogate markers of
proliferation such as serum PSA and free
testosterone was observed
G. max Preparations of unconjugated soy Oral administration of soy isoflavones (PTI Phase I clinical trial (100)
isoflavones, PTI G-2535 and PTI G- G-2535 and PTI G-4660) (2, 4, or 8 mg/kg
4660 (which contain 43% and 90% orally for 1 week) gives plasma
genistein, respectively) concentrations of genistein that have
been associated with
antimetastatic activity
G. max 60-g soy supplement (containing In women (n ¼ 48) with breast disease, the Double-blind, randomized,
45 mg isoflavones) taken daily for proliferation rate of breast lobular controlled trial (101)
14 days epithelium significantly increased after 14
days of soy supplementation when both
the day of menstrual cycle and the age
of patient were accounted for. Short-
term dietary soy stimulates breast
proliferation
Malva sylvestris L. (Malvaceae) The dry flowers of M. sylvestris Patients were asked to take their Randomized, double-arm, open-
powders were mixed together in a medication three times per day (before label, active-controlled
proportion of 1:1, and filled into breakfast, lunch, dinner, or before clinical trial
sachets weighing 4 g bedtime) for four weeks. They were (NCT02854358) (102)
asked to mix the content of a sachet in a
glass of boiled water (250 mL) as one
dose. The M. sylvestris preparation should
be considered as a suitable treatment for
xerostomia and improving QoL in
HNC patients
M. sylvestris Herbal compound (4 g in sachets The herbal group patients showed a Randomized clinical trial (103)
containing equal portions of M. significant difference between the grade
sylvestris and Alcea digitata (Boiss.) of dry mouth before and after
Alef.) was administered 3 times per intervention, in a total of 62 subjects,
day for 4 weeks supporting the efficacy of the herbal
compound for controlling symptoms of
dry mouth in HNC patients
Momordica charantia L. Not reported In 30 cervical cancer patients undergoing Double-blind, randomized,
(Cucurbitaceae) radiotherapy, an increased percentage of placebo-controlled trial (104)
NK cells in patients treatment group
(bitter melon ingestion), and a significant
decrease of P-glycoprotein levels
were observed
Morus nigra L. (Moraceae) Black mulberries were boiled with The experimental group (n ¼ 38) rinsed Randomized controlled
water (the ratio of blackberry and their mouths with black mulberry study (105)
water is 1:1) molasses for a few minutes (1–3 min)
and swallowed it three times a day:
15–20 min before radiotherapy,
15–20 min following, and again, 6 hours
later. This study showed that black
mulberry molasses usage was an
effective intervention in preventing the
radiation-induced mucositis of
HNC patients
Phyllanthus Urinaria L. Formulation containing P. Urinaria A total of 102 cirrhosis patients took 100 mL Double-blind, randomized,
(Phyllanthaceae) and (Guangdong Yifang Pharmaceutical, of the medicine in the morning and placebo-controlled trial (106)
C. longa China) (P. urinaria 30 g and C. longa evening, 20 days per month for 3 years,
15 g) was dissolved in 200 mL and it showed to be useful in preventing
of water or delaying the development of
preneoplastic hepatitis B virus-associated
hepatocellular carcinoma
P. granatum 900 mg of an Ellagitannins-containing The consumption of the extract by 35 Randomized clinical trial (107)
pomegranate extract ingested for colorectal cancer patients was
5–35 days significantly associated with a decreased
effect in the expression of CD44 (cell
surface adhesion receptor), CTNNB1
(Catenin Beta 1), CDKN1A (Cyclin
Dependent Kinase Inhibitor 1A), TYMS
(Thymidylate Synthetase) and EGFR,
(Continued)
Table 1. Continued.
colorectal cancer-related genes,
suggesting that the intake of this extract
modulated the impact on
gene expression
P. granatum Pomegranate extract 900 mg/day for Significant levels of ellagic acid derivatives Double-blind, randomized,
15 days before surgical resection and urolithins are found in human colon placebo-controlled trial (108)
tissues from colorectal cancer patients (n (CICYT-AGL2011-22447)
¼ 52) after the consumption of
pomegranate. It is suggested that ellagic
acid and urolithins can exert
chemopreventive activity
P. granatum Patients received 1 or 3 g/day of Pomegranate extract treatment was Randomized phase II
pomegranate extract for up to associated with 6 month increases in (NCT01220817) (109)
18 months PSA levels, doubling treatment time
without adverse effects
Ruta graveolens L. (Rutaceae) Oral treatment consisted of two 1-mL Some of the 31 patients with locally- Single-centre, open-label,
ampoules of R. graveolens (9c advanced solid tumors or metastases, uncontrolled, pilot (110)
dilution) given daily for a minimum previously treated with all available
of 8 weeks standard anti-cancer treatments, had a
transitory improvement in QoL with a
median survival of 6.7 months after
treated with R. graveolens 9c
Trifolium pratense 40 mg red clover isoflavone dietary The study supports that treatment with red Randomized, double-blind,
L. (Fabaceae) supplement taken daily for clover isoflavones is safe and well- placebo-controlled pilot
three years tolerated in women with a family history trial (111)
of breast cancer
T. pratense Each participant was instructed to The ratio of 2-hydroxyestrone to 16 alpha- Trial pilot study (112)
take 3 tablets containing 50 mg hydroxyestrone (proposed marker of
isoflavones from red clover breast cancer risk), showed a statistically
(Estrofactors, CA) once a day with significant decrease by using this
food for 12 weeks combination isoflavone
nutritional supplement
T. pratense Ingestion of 4 tablets/day of Trinovin In 20 Asian men, this study suggests that Nonrandomized, nonblinded
(Novogen, Australia) containing dietary isoflavones may halt prostate trial (113)
40 mg of standardized red clover cancer progression by inducing apoptosis
in low to moderate-grade tumors,
potentially contributing to a lower
incidence of clinically significant disease
Uncaria tomentosa (Willd. ex 100 mg dose of a dry extract of U. In 51 patients with advanced solid tumors Prospective phase II (114)
Schult.) DC. (Rubiaceae) tomentosa three times per day who had no further therapeutic options
and a life expectancy of at least 2
months, the use of cat’s claw was
beneficial, improving their QoL and
reducing fatigue
U. tomentosa 3 tablets with aqueous U. tomentosa In 40 Patients with invasive ductal Randomized clinical trial (115)
extract (100 mg/tablet) (Herbarium) carcinoma-stage II, U. tomentosa reduced
per day during 6 chemotherapy the neutropenia caused by chemotherapy
cycles of 21 days each and was also able to restore cellular DNA
damage. The extract is an effective
adjuvant treatment for breast cancer
Zingiber officinale Roscoe 1.2 g of standardized ginger extract Adjuvant ginger supplementation is Double-Blind, randomized,
(Zingiberaceae) per day, in addition to standard associated with better chemotherapy- placebo-controlled trial (116)
antiemetic therapy, during the first induced nausea-related QoL and less
three cycles of chemotherapy cancer-related fatigue
Z. officinale 6-gingerol 10 mg orally twice daily for In 42 patients treated with 6-gingerol, Phase II, randomized, double-
12 weeks significantly less grade 3 fatigue was blind, placebo-
reported. 6-Gingerol considerably controlled (117)
improved the overall complete response
rate of CINV, appetite, and QoL in cancer
patients receiving adjuvant
chemotherapy
Z. officinale Patients inhaled a blend of 1.0 mL In 71 patients with differentiated thyroid Randomized, controlled
lemon and 0.5 mL ginger essential cancer undergoing radioactive iodine trial (118)
oils for 10 min during admission therapy, an improvement of salivary
gland function was observed, suggesting
the efficacy of aromatherapy in the
prevention of treatment-related salivary
gland disorder
Z. officinale 500 mg powder ginger, mixed with a Severe nausea and vomiting episodes were Randomized, controlled
spoonful of yogurt, twice a day for significantly lower in patients in the trial (119)
(Continued)
Table 1. Continued.
three days, ingested 30 minutes study group (powder ginger) (n ¼ 30) in
before chemotherapy comparison to the control group
administration
Z. officinale Wrist-ankle acupuncture and ginger The combined treatment could prevent Randomized, controlled
moxibustion used once for 30 min gastrointestinal tract reactions to trial (120)
before the daily chemotherapy chemotherapy in a total of 30 patients
with gynecological tumors. In addition,
the proposed method had fewer side
effects, lower cost, and less risk
Z. officinale 250 mg ginger powder capsules In 40 women undergoing chemotherapy, Randomized, double-blind,
(Zintoma) ingested 4 times a day ginger capsules accompanied by the placebo-controlled clinical
(1 g/day) for 6 days starting 3 days antiemetic routine treatment could trial (121)
before chemotherapy session relieve chemotherapy-induced vomiting
in all chemotherapy phases
Z. officinale 4 capsules of ginger/day (each capsule In 10 women diagnosed with breast cancer, Randomized, double-blind,
containing 750 mg) for 6 weeks ginger supplementation alone or in placebo-controlled clinical
combination with water-based exercise trial (122)
played an important role in the
pathogenesis of oxidative stress in obese
women, and is a non-drug therapeutic
strategy to reduce systemic stress
Z. officinale Routine antiemetic drugs along with 4 In the 22 subjects under chemotherapy Randomized, cross-over clinical
ginger capsules (250 mg ginger treatment receiving ginger capsules (two trial (123)
capsule) (Zintoma, Iran) capsules taken 30 minutes before
chemotherapy and the other capsules
6 hours after chemotherapy for least 28
days, during two episodes), a significant
reduction in frequency and intensity of
nausea and vomiting was observed
Z. officinale 2 g of ginger ingested daily for Ginger may reduce proliferation in the Pilot, randomized, controlled
28 days normal-appearing colorectal epithelium trial (124)
and increase apoptosis and
differentiation relative to proliferation,
especially in the differentiation zone of
the crypts, which supports a larger study
Z. officinale Ginger (1.5 g/day in 3 divided doses In 50 women with advanced breast cancer, Pilot, randomized, open-label
every 8 hours) plus standard adding ginger to the standard antiemetic clinical trial (125)
antiemetic regimen (granisetron therapy effectively reduced the
plus dexamethasone) prevalence of nausea from 6 to 24 hours
post-chemotherapy
Z. officinale Three capsules of ginger (250 mg) In a total of 576 adult cancer patients, Double-blind, multicenter
twice daily for 6 days, starting 3 ginger supplementation with a daily trial (126)
days before the first day of dose of 0.5 g–1.0 g showed to
chemotherapy significantly help reducing the severity of
acute chemotherapy-induced nausea
Z. officinale Ginger root powder capsules ingested Ginger root powder was effective in Randomized, double-blind,
on days 1 to 3 of the delaying and reducing the severity of placebo-controlled clinical
chemotherapy cycle (20–40 kg in acute CINV as additional therapy to trial (NCT00940368) (127)
weight 6 capsules/day ondansetron (antiemetic) and
containing 167 mg of ginger; dexamethasone in bone sarcoma patients
40–60 kg in weight 5 capsules/ receiving high emetogenic chemotherapy
day containing 400 mg of ginger)
Z. officinale A protein drink and ginger (four 250- High protein meals with ginger reduced the Randomized, double-blind,
mg capsules of dried powdered delayed nausea of chemotherapy in 28 placebo-controlled clinical
ginger root (ZintonaVR )) ingested patients with cancer and reduced the use trial (128)
twice daily for 3 days, beginning of antiemetic medications. Protein with
the day after their chemotherapy ginger holds the potential of
representing a novel, nutritionally based
treatment for the delayed nausea of
chemotherapy
Source: Research data, 2018.
studies, besides C. longa and Z. officinale with 13 However, it demonstrates promising potential, a fact
studies each, the last two plants belonging to the confirmed in this study, since seven searches indexed
Zingiberaceae family. Curcumin, a low molecular in MEDLINE/PubMed report therapeutic properties
weight polyphenol found in high concentration in attributed to curcumin (65,79,81,83,86–87,92).
plants of the Zingiberaceae family species (129), has As observed in the 76 clinical trials in humans
not been fully elucidated in cancer clinical trials. listed in Table 1, there are studies on 19 different
forms of cancer. The prostate was the organ with the of nausea and the number of vomiting episodes.
highest concentration of clinical trials involving Studies suggest that ginger and its active compounds
RENISUS plants/compounds, 12 articles, followed by may increase digestive responsiveness and speed stom-
HNC, with seven surveys, and breast with six clinical ach emptying, reducing vomiting. The spice has anti-
studies. In general, clinical trials revealed an adjuvant inflammatory properties, which may improve diges-
role of plant/compound treatments in reducing serum tion and support the release of blood-pressure-regulat-
PSA levels in patients with prostate cancer, and G. ing hormones to calm the body and minimize
max (88–90,93,95–99) was the most evaluated plant in nausea (133).
this form of cancer. In patients with HNC, the use of Another significant side effect is OM, a common
mouthwash containing RENISUS plants/compounds complication of cancer chemotherapy. It usually
was the most evaluated form, focusing on OM treat- begins 5–10 day after starting chemotherapy and lasts
ment (64,71,82,105), one of the most significant side 7–14 day. This oral mucosa inflammation causes the
effects of cancer therapy that, to varying degrees, mucosal lining of the mouth to atrophy and decom-
affects approximately 85% of patients undergoing pose, forming ulcers. Many different substances were
radiotherapy or chemotherapy. Moreover, in patients used separately to treat or prevent OM, but no stand-
with breast cancer, the prophylactic use of RENISUS ard procedure was established as definitive (134).
plant species is suggested to reduce side effects such There are good results with plants in the prevention/
as vomiting frequency and relieving nausea induced treatment of OM, the clinical tests described in Table
by chemotherapy (76,121,126), besides lowering the 1 indicate that the species A. millefolium (53), B.
intensity of radiation-induced dermatitis (66,67,73). pilosa (71), M. chamomilla (74,76), M. piperita (74)
Skin lesions usually emerge after the second week of and C. longa (77,81) exerted levels of therapeutic
treatment and appear at different levels, affecting up activity against OM. It is described that the main
to 95% of patients undergoing radiotherapy, a fact active compound of C. longa, curcumin, accelerates
that justifies clinical trials to seek to reduce the inten- wound healing, decreases oxidative stress, modulates
sity of dermatitis. inflammatory response, and reduces the release of dif-
Because cancer is a treatable but still incurable dis- ferent interleukins through inhibition of nuclear factor
ease, we have to take into account that numerous clin- jappa-B (NFjB) (135). The rationale that OM patho-
ical trials seek to mitigate adverse effects and promote genesis involves the activation of NFjB, initiating an
patients’ wellness. Nausea and vomiting are some of inflammatory response and increasing sub-epithelial
the most common side effects of the treatment, specif- vascularity, suggests that curcumin may represent a
ically induced by chemotherapy (130). The effects are potential therapeutic agent against mucositis (71).
peculiar but usually begin within one to two hours of All of these side effects described significantly affect
chemotherapy, and the peaks are up to four to six patients’ QoL. Experiencing a potentially fatal disease
hours later. Further, such effects may occur more such as cancer and its treatment-related problems
than 24 h, after chemotherapy or even prior to treat- usually causes beyond pain, fear, and survival means a
ment as a conditioned response in patients who have variety of changes in patients’ QoL (136). In this
developed significant nausea and vomiting during pre- sense, seven studies with six distinct plants, C. longa
vious cycles of chemotherapy (131). Even with the (81), G. max (91), M. sylvestris (102), R. graveolens
administration of antiemetic drugs considered effect- (110), U. tomentosa (114), and Z. officinale (116,117),
ive, inadequate control of CINV can persist until days showed beneficial effects on the QoL of patients
after treatment, resulting in dehydration, malnutrition, affected by cancer, which include more extended sur-
aspiration pneumonia, increased hospitalization rates, vival period, reduced fatigue, and improved appetite.
and even treatment discontinuation. Therefore, effect- Since one of the focuses of this review was to
ive and well-tolerated antiemetic therapy is essential evaluate scientific research on cancer and plants in
for patients receiving chemotherapy (132). In this clinical trials, in addition to the MEDLINE/PubMed
review, we observe that several clinical trials have database, studies on the ClinicalTrials.gov portal were
evaluated the response of plants/compounds to CINV analyzed. Thus, Table 2 presents details of human
(75,116,117,120,123,125–128) in isolation or combin- studies involving RENISUS plants/compounds indexed
ation with antiemetic agents. Many of these studies at ClinicalTrials.gov. The results found (Table 2) are
were performed with ginger similar to the data selected from the MEDLINE/
(116,117,119,123,125–128), revealing an adjuvant role PubMed database (Table 1). The three plants with the
of ginger supplementation and attenuating the severity largest number of studies are the same, G. max (six
Table 2. Main details of human clinical studies published on ClinicalTrials.gov with RENISUS plants/compounds.
Status Study Details Conditions Interventions
Completed This phase II trial studied curcumin (C. longa compound) in Prevalent Subclinical Neoplastic Pharmacological study;
Has Results preventing colon cancer in smokers with aberrant crypt Lesions (Aberrant Crypt Foci) curcumin (137)
(NCT00365209) foci. A total of 44 patients received 2 or 4 grams of oral
curcumin once a day. Treatment continued for up to 30
days in the absence of acceptable toxicity or disease
progression
Completed 35 patients ingested curcumin (four 500 mg capsules three Breast Cancer Curcumin C3 Complex (138)
Has Results times daily by mouth) for the prescribed course of
(NCT01042938) radiation treatment (4–7 weeks). This clinical pilot study
showed that curcumin decreased acute radiation-induced
dermatitis during postoperative radiotherapy for
breast cancer
Completed The purpose was to determine whether curcumin can Dermatitis Curcumin compound (139)
Has Results prevent or reduce the severity of dermatitis caused by
(NCT01246973) radiation therapy. In 686 patients, four Curcumin C3
Complex 500 mg capsules (2.0 g) were taken orally 3
times/day throughout radiation treatment. Curcumin is
nontoxic and has been found to enhance the functions of
normal tissues
Completed This randomized phase II trial studied curcumin in treating Familial Adenomatous Polyposis Curcumin; Laboratory Biomarker
Has Results patients with familial adenomatous polyposis. 44 patients Analysis (140)
(NCT00641147) received curcumin orally twice daily for 12 months.
Curcumin may prevent colorectal cancer in patients with
a history of rectal polyps or colorectal neoplasia.
Completed Phase II double-blind, controlled trial involved adults OM Neem Mouthrinse (141)
Has Results receiving radiation therapy for HNC. Participants rinsed
(NCT01898091) their mouth for 30 seconds with the 10 mL dose of the
assigned mouthrinse (including aloe and peppermint),
three times per day, for approximately 7 weeks during
radiation therapy. The mouthrinse lessens OM
Completed Phase II trial studied how well giving vitamin D together Prostate Cancer Dietary Supplement: Vitamin D;
Has Results with soy supplements (G. max) works in treating patients Dietary Supplement:
(NCT00499408) (n ¼ 26) with recurrent prostate cancer. Patients received soy (142)
oral supplementation with vitamin D (cholecalciferol) and
soy (160 mg soy isoflavones per day). Participants showed
a 50% reduction in PSA level during treatment
Completed Randomized study phase III with 86 patients, who randomly Prostate Neoplasm Soy Supplement (143)
Has Results received 4 capsules twice a day (8 capsules) with either
(NCT00255125) water or juice (except grapefruit juice), a placebo for 2–4
weeks before the planned surgery for their prostate
cancer treatment. The study showed the protective effect
a commercial soy supplement has on prostate cancer and
healthy prostate tissue
Terminated This randomized phase III study examined soy protein/ Hot Flashes; Prostate Cancer Soy protein/isoflavones oral
Has Results isoflavones and venlafaxine in the severity score of hot powder supplement (144)
(NCT00354432) flash symptoms in patients (n ¼ 120) submitted to
hormonal manipulation for prostate cancer treatment.
Patients received soy protein powder (20 g) orally, 160 mg
total isoflavones isocaloric supplement of casein protein.
Soy protein improved measures of QoL
Completed Phase IV research analyzed the effects of a soy supplement Hot Flashes; Prostate cancer Isoflavone (145)
Has Results called Revival in men with prostate cancer undergoing
(NCT00245518) Androgen Deprivation Therapy. Participants (n ¼ 39) were
asked to take their supplement once/day for 14 weeks.
Possible benefits may include an increase in memory,
decrease in hot flashes, and a general increase in QoL
Completed This phase II clinical trial studied how well soy isoflavones Hypopharyngeal and Laryngeal Laboratory Biomarker Analysis;
Has Results work in preventing HNC in patients with stage I-IV head Squamous Cell Carcinoma Soy Isoflavones (146)
(NCT02007200) and neck cancer undergoing surgery. Patients received
soy isoflavones orally for approximately 14 days before
undergoing surgery. The use of soy isoflavones may
prevent HNC recurrence
Completed Phase II Clinical Trial recruited and treated 96 men Prostate Cancer Purified isoflavones And Methyl
Has Results diagnosed with prostate cancer and scheduled for cellulose blend (147)
(NCT01036321) prostatectomy. They took a capsule form of either purified
isoflavones for a 3–6 weeks period (two capsules daily, at
breakfast and dinner). In the day of pre-operative surgery,
when blood exams were made, they were asked to take
the second dose with lunch. Isoflavones showed being
able to slow the progression of prostate cancer
(Continued)
Table 2. Continued.
Status Study Details Conditions Interventions
Completed This 9-week phase III, multi-center, double-blind, placebo- Pain; Advanced Cancer Nabiximols (148)
Has Results controlled study aimed to determine the efficacy, safety,
(NCT01361607) and tolerability of nabiximols (SativexV R ) spray (containing
peppermint oil (0.05%) flavoring) as an adjunctive

treatment in relieving persistent chronic pain in
participants with advanced cancer. Nabiximols was self-
administered by participants (n ¼ 399) as a 100 lL
oromucosal spray in the morning and evening, up to a
maximum of 10 sprays per day for 5 weeks
Completed This phase II study analyzed if ginger root extract (Z. Colorectal Cancer Ginger Root Extract (Pure
Has Results officinale) 2.0 g per day (10:1 extract, 5% - Gingerols), Encapsulations) (124)
(NCT01344538) when taken daily for 28 days, can lower levels of
eicosanoids. Results suggest that ginger may reduce
proliferation in the normal-appearing colorectal
epithelium and increase apoptosis and differentiation
relative to proliferation - especially in the differentiation
zone of the crypts
Completed This randomized phase II/III trial evaluated the administration Nausea and vomiting Dietary Supplement:
Has Results of antiemetic drugs along with ginger to assess their ginger (149)
(NCT00040742) good performance compared to antiemetic drugs isolated
in the treatment of nausea in patients receiving
chemotherapy for cancer. Patients received oral doses of
ginger (0.5 g) twice daily on days 3 to 3 of
chemotherapy courses 2 and 3
studies (142–147)), C. longa (four tests (137–140)), antitumor effects by modulating the genes related to
and Z. officinale (two surveys (124,149)). Similarly, cell cycle control and apoptosis (152).
prostate cancer was again the most studied form of Once clinical trials are completed, and the results
the disease (five clinical trials (142–145,147)), there show a molecule is nontoxic and effective, it can be
are also researches for colorectal cancer (three studies approved for marketing by regulatory authorities.
(128,131,139)) and HNCs (two studies (141,146)), for That typically is the starting point of a drug’s period
example. It should be noted that the clinical trials; of market exclusivity, which is determined by the
that have four phases: I, II, III, and IV; evaluate valid patent term (153). In this sense, adding the
whether the tests or treatments are safe and work in terms ‘plant’ and ‘cancer’ in the EPO patent database
humans (150). Regarding the researches selected in generated 663 results, and in the WIPO Patentscope
Table 2, seven studies are in Phase II database, there are 665 results. We refined the search
(124,137,140–142,146–148); this phase evaluates the and added as terms the scientific names of the 71
substances’ efficacy and side effects. Three other more medicinal plants listed in RENISUS, in addition to the
advanced studies are in Phase III (143,144,148), which descriptors ‘cancer,’ ‘malignant tumor,’ ‘carcinoma,’
analyzes the effectiveness and monitors adverse reac- ‘neoplasia.’ The search resulted in 231 patents in the
tions. There is a pilot clinical study (138) and a Phase EPO database and 279 in the WIPO database, and
II/III one (149). There is also a Phase IV study (145), included all types of studies. The reviewers analyzed
a pharmacovigilance stage after the drug has already each patent to select those that already had tests in
been approved and brought to the market, this phase patients (Table 3).
analyzes additional details on safety, efficacy, and risk New formulations, methods of use or manufactur-
factors. Clinical trials begin after a compound/formu- ing, and compounds of plant species listed in
lation shows favorable and promising results in the RENISUS protected by current forms of intellectual
face of rigorous preclinical development work involv- property have had the most significant number of
ing laboratory (chemical/biological/pharmacological/ clinical studies indexed in the MEDLINE/PubMed
toxicological) tests (151). At this stage of research, (Table 1) and ClinicalTrials.gov databases (Table 2).
extracts are scarce, and compounds or formulations Comparatively, all 26 patents selected in Table 3 are
are usually evaluated. This fact is observed in the related to new formulations (16 patents), methods of
researches in Table 2, only one research analyzed the use or manufacturing (nine patents), and compounds
plant extract (ginger root extract) (124), and ten stud- of plant species (one patent). After verifying effective-
ies tested the activity of compounds (curcumin ness in clinical trials data, results shown in Tables 1
(137–140) and isoflavone (142–147)). These results and 2, one of the objectives of industries and
may be associated with the fact that isoflavone exerts researchers is to apply for patent protection. Thus, the
Table 3. Examples of patents registered and available for consultation in the European Patent Office and at WIPO Patentscope,
involving formulations or compounds of plants of RENISUS.
Application number EPO/WIPO Plant Summary of the invention/application Database
CN20151378622 A. millefolium The invention including A. millefolium provides EPO (154)
an alternative for treating pancreatic cancer.
Used for reducing lumps, controlling the
diffusion and transfer of cancer cells. No side
effects were caused, and the achieved results
include relieving patients’ pains, stabilizing
disease conditions, prolonging the survival
period, and increasing the proportion of
patients achieving complete
clinical remission
CN201610685424 and A. sativum The invention relates to an active polypeptide EPO/WIPO (155)
102016000685424 separated from A. sativum and the amino
acid sequences of the active polypeptide.
The polypeptide has a good effect on
treating breast cancer and has no toxic and
side effects on normal cells at the same time
JP19970215224 and 21522497 A. sativum and Z. officinale New substance originated from vegetables, EPO/WIPO (156)
possible to be extracted with organic
solvents. This substance originated from
vegetables such as A. sativum or Z. officinale,
has a selective proliferation-inhibiting
activity, and can be used for treating uterine
cervical cancer, vulvar cancer, penile cancer,
laryngeal cancer, and carcinoma cutaneum
WO2003IB01885 and 2003230085 A. sativum, C. longa, and G. max New polyherbal formulation has been found to EPO/WIPO (157)
be effective for the treatment of
adenocarcinoma of the prostate. The
formulation comprises a mixture of the
following herbs: G. max, A. Sativum, and C.
longa, or a mixture of the active ingredients
extracted from those herbs
CN2009157175 and 200910057175.5 Aloe barbadensis Mill. The invention relates to a new pharmacologic EPO/WIPO (158)
application of aloe polysaccharide, that is
used to prepare medicines for inhibiting the
proliferation of hepatoma cells or combined
with other antitumor medicine combinations
to prepare compounds for reducing the
clinical toxic or side effects of
chemotherapy medicines
US20040895772 and 10895772 A. barbadensis and G. max A pharmaceutical or medicinal preparation EPO/WIPO (159)
comprising a mixture containing among
other species A. Barbedensis and G. Max, or a
mixture of the active ingredients and is
effective for the treatment of human cancer,
in particular, refractory leukemias,
lymphomas, myelodysplastic syndrome, and
aplastic anemias
CA20162967506 and PCT/ A. vera and A. sativum This patent is related to the treatment of HPV, EPO/WIPO (160)
SA2016/000001 which may cause different kinds of cancer. A
composition that helps to eliminate this virus
as soon as it appears on the skin was
created. The most important ingredient of
this remedy is a herbal combination
consisting of A.Vera, Citrullus colocynthis (L.)
Schrad, hard sea salt, myrrh, and garlic
RU20130127633 and 2013127633/15 A. vera The invention relates to a method of preparing EPO/WIPO (161)
fine-grained powder of aloe extract with
immunomodulating and anticancer
properties containing extract of A.vera and
pharmaceutical preservatives. The use is
projected to prepare a drug for treating one
or more types of cancer, comprising
leukemia, lymphoma, prostate cancer, breast
cancer, and colon cancer
CN20171848728 and B. pilosa and Z. officinale The invention discloses a Traditional Chinese EPO/WIPO (162)
201710848728.3 Medicine (TCM) composition used for
treating stomach cancer. TCM composition
comprises among other plants, 1 to 5 g of B.
pilosa and 5 to 9 parts of ginger. TCM
composition possesses anticancer activity
(Continued)
Table 3. Continued.
CN201610713483 and B. pilosa The invention discloses a TCM composition for EPO/WIPO (163)
102016000713483 treating stomach cancer and comprises
among other plants, 10–20 parts of B. pilosa.
TCM composition has the effects of tonifying,
clearing toxic materials, and relieving
patients’ pain effectively and improving QoL
CN20141563828 and B. pilosa The invention discloses a TCM preparation for EPO/WIPO (164)
201410563828.8 treating rectal cancer and comprises, among
other plants, B. pilosa and showed high
safety and reliability, no toxic and side
effects and it can achieve the purpose of
treating both symptoms and causes
US20020274596 Chenopodium ambrosioides L. Method of treating abnormal growths in a EPO (165)
patient that include tumors, fibroids, cysts,
and cystadenomas. Dry leaves and stalks of a
C. ambrosioides plant are made into a dried
tea. The tea was administered daily. The
method also reduces high PSA levels
WO2018EP57076 and PCT/ Copaifera L. The invention relates to the use of Copaifera EPO (166)
EP2018/057076 oleoresin for producing a medicament for
preventing and treating pathologies of the
prostate, particularly benign prostatic
hyperplasia and prostate cancer
CN20161189976 C. longa and A. sativum The invention discloses a medicine for treating EPO (167)
rectal cancer and a preparation method that
comprises the following components in parts
by weight: 3–5 parts of C. longa and 1–3
parts of garlic extract. The medicine can
achieve the effects of preventing tumors and
inhibiting cancer cells growth
KR20100084268 and C. longa A composition containing C. longa as an active EPO/WIPO (168)
1020100084268 ingredient (used in the form of a capsule,
liquid, or suspension) is provided to suppress
prostate cancer cell growth and induce cell
apoptosis, administered beside other therapy
such as radiation or chemotherapy
201510266303.2 C. longa The invention discloses a TCM preparation for WIPO (169)
relieving ovary choriocarcinoma including,
among other plant species, C. longa; it plays
a role in controlling and relieving the human
ovary choriocarcinoma
201510422413.3 C. longa L. and U. tomentosa The invention provides a TCM composition for WIPO (170)
treating gastric cancer and mainly comprises
5–25 parts of C. longa, 10–20 parts of
Uncaria. The invention was effective in
treating and reducing drug resistance, and
reducing side effects of chemotherapy
US20040853220 and 1,08,53,220 G. max A process of using a fermented G. max extract EPO/WIPO (171)
used for enhancing NK cells activity and
inhibitory activities to GABA (Gamma-Amino
Butyric Acid) for prolonging sleeping time
and reducing fatigue in cancer patients
during chemotherapy was conducted
TW20040114722 G. max A manufacturing method of fermented soybean EPO (172)
extract that can inhibit the combination of
glutamate receptor of neural cells and N-
methyl-D-aspartate (NMDA), besides
prolonging the sleeping time induced by
pentobarbital and reducing tiredness of
cancer patients induced by chemotherapy
CN2004158419 and 200410058419.9 G. max The invention relates to a method for utilizing EPO/WIPO (173)
fermented soybean extract of G. max that
can inhibit the bonding between nerve cell
glutacid receptor and NMDA, extend the
sleeping time and lower sense of fatigue for
patients with cancer during chemotherapy
AU20160101447 and 2,01,61,01,447 P. amarus The present invention relates to a method for EPO/WIPO (174)
treating a subject suffering from liver cancer
that comprises administrating synergistic
amounts of a P. amarus extract and 5-
fluorouracil or a prodrug 5-fluorouracil.
(Continued)
Table 3. Continued.
Combined administration represents a highly
promising treatment option for treating
patients while reducing or preventing
resistances
CN20161517509 and P. urinaria The invention provides a compound P. urinaria EPO/WIPO (175)
10,20,16,00,05,17,509 (10–50 g) TCM composition for treating
precancerous lesions of hepatitis B and
comprises an effective ingredient and
medically acceptable auxiliaries. The
composition can effectively be used to
inhibit precancerous variation hyperplasia,
and effectively delay precancerous lesions of
liver cancer related to viral hepatitis B
CN20141608377 and T. pratense The invention discloses a preparation method EPO/WIPO (176)
201410608377.5 of a nasopharynx cancer chemoradiotherapy
assisting skin ointment characterized by
comprising the aqueous extraction of T.
pratense among other plant species. The
clinical experiments show that the skin
ointment is synergetic with the
chemotherapy, good in curative effect
and safe
RU20150102002 and 2015102002 Z. officinale Composition for cancer patients’ QoL EPO/WIPO (177)
improvement is presented. Containing
lipophilic extract of ginger (Z. officinale
extract is obtained from roots and rhizomes),
among other plants, and a phospholipid
complex of silybin, with phospholipids
selected from soybean lecithin, it is effective
for cancer patients’ QoL improvement
RU20130103334 and 2013103334/15 Z. officinale The invention relates to composition and EPO/WIPO (178)
combination containing gingerol from Z.
officinale. The composition is effective for
treating itch, peripheral pain, radiation
dermatitis caused by radiotherapy for cancer,
edema, and skin irradiation conditions
JP19830132782 Z. officinale Extracting a crude drug composed of SHOKYO EPO (179)
(rhizome of Z. officinale) to provide an
effective agent to inhibit the fat
decomposition accelerating action of cancer
toxin (toxohormone L) and promote the lipid
metabolism and appetite of the cancer
patient. The agent has low toxicity and high
safety. Expected dose: 2–10 g per dose and
< ¼3 doses a day for adults
data presented in Table 3 corroborates these results, chemotherapy (168). Concerning gastrointestinal tract
because the plants most involved in patent applica- cancers, there are patents on the preparation of an
tions were also those with the most substantial ointment for the collateral effects induced by chemo-
amount of clinical researches (Tables 1 and 2). A. sati- radiotherapy of nasopharyngeal cancer (176). The
vum (155–157,160,167), C. longa (157,167–170), G. TCM composition containing B. pilosa, used in the
max (157,159,171,173), and Z. officinale stomach cancer treatment, is capable of inhibiting
(156,162,174–179) have five patents with therapeutic tumor growth (162,163). Another TCM composition
applications aimed at cancer treatment (Table 3). For containing C. longa and U. tomentosa, used in the
adjuvant prostate cancer treatments, there are investi- gastric cancer treatment, reduces the side effects of
gations with herbal formulations or a compound of chemotherapy (170). Besides, new pharmacological
the active ingredients for treating adenocarcinomas applications with polysaccharide of A. barbadensis are
(157), method of preparation of powder from A. vera used to inhibit the proliferation of human hepatoma
extract (161), use of oleoresin in the composition of a and reduce the effects of chemotherapy, also increas-
medicament (166). There is also a patent application ing the effect of antitumor drugs (158). There are also
of a plant composition as an active ingredient used in patents of other TCM compositions preparation; the
the form of a tablet to induce the apoptosis mechan- first comprises P. urinary, among other plant species,
ism, taken in conjunction with radiotherapy or and can be used to effectively inhibit precancerous
liver hyperplasia related to viral hepatitis B (175). The of complementary therapies in clinical settings can
second preparation comprises B. pilosa, among other help maximize benefits, minimize risk, and facilitate
plants, to treat symptoms and causes of human rectal their safe and effective integration in conventional
cancer (164). Another drug containing C. longa and cancer treatment.
garlic, among other components, has effects on the
prevention and inhibition of rectal tumors
growth (167). Conclusion
TCM professionals use herbal medicines and vari- We selected studies on 19 different forms of cancer,
ous mental and bodily practices to treat or prevent among clinical trials and patents. The prostate was the
health problems. Outside China, people use TCM pri-
organ with the highest incidence of clinical trials
marily as a complementary health approach (180). Six
involving RENISUS plants such as G. max, C. longa,
patents (162–164,169,170,175) of therapeutic applica-
and Z. officinale, and phytochemicals such as curcu-
tions for cancer use TCM. In view of the results
min and soy isoflavone.
described, plants are demonstrating to be useful and
We observed that several clinical trials have eval-
effective in sensitizing conventional cancer treatments,
uated the response of plants/compounds to chemo-
attenuating side effects of chemotherapy, and improv-
therapy-induced nausea and vomiting alone or in
ing patients’ QoL (181). A study with 453 cancer
combination with antiemetic agents. Many of these
patients revealed that the percentage of patients who
studies were performed with ginger, revealing an adju-
used a combination of conventional chemotherapy
vant role of this plant. There are also good results
and herbal medicines was approximately 77% (182).
with plants in the prevention/treatment of OM, indi-
This search for complementary therapies is due in
part to the fact that the traditional treatments used in cating that the species A. millefolium, B. pilosa, M.
the clinic, in addition to adverse effects, present flaws chamomilla, M. piperita, and C. longa exerted levels of
in therapeutic responses, creating a significant chal- therapeutic activity against OM, and that the plant
lenge for science (183). Thus, new therapeutic alterna- species C. longa, G. max, M. sylvestris, R. graveolens,
tives that aim to mitigate disease progression with U. tomentosa and Z. officinale exert beneficial effects
fewer side effects and more effective responses, such on the QoL of patients with cancer.
as Clustered Regularly Interspaced Short Palindromic
Repeats (CRISPR), promise to accelerate cancer
research, providing an efficient technology for dissect-
Author contribution statement
ing tumor mechanisms and identifying targets for We declare that we all have made substantial contri-
drug development (184). Many clinical trials are butions to the conception or design of the work; or
studying forms of immunotherapies. These treatments the acquisition, analysis, or interpretation of data for
strive to stimulate the natural defenses to fight cancer the work.
using substances produced by the body, or in the D.J.Marmitt and C.Rempel conceived and designed
laboratory, to improve or restore the immune system the study. D.J.Marmitt and G.R.Silva performed the
function, which has been a key strategy in cancer analyses. D.J.Marmitt and S.Bitencourt analyzed the
immunotherapy. This “immune enhancement” strat- data. D.J.Marmitt, S.Bitencourt and M.Goettert wrote
egy generally results in more objective responses with the paper. C.Rempel and M.Goettert critically revised
decreased immune-related adverse events (185). the manuscript.
Patients report that they seek therapeutic alterna-
tives to treat symptoms and adverse effects, improve
QoL, and deal with the needs not met by the conven- Disclosure statement
tional medical care (186). Although these therapies The authors report no conflict of interest.
may provide benefits to patients, many plants have
not been rigorously studied for safety or efficacy.
Some plants/compounds may interact with conven- Funding
tional therapies or contain harmful substances in
This work was supported by Univates, Fundaç~ao de Auxılio
long-term use (187). Despite the high prevalence of a Pesquisa do Estado do Rio Grande do Sul (FAPERGS).
these complementary therapies use, research suggests This study was financed in part by the Coordenaç~ao de
that patients often do not discuss their application Aperfeiçoamento de Pessoal de Nıvel Superior – Brasil
with their physician (188). Thus, considering the use (CAPES) Finance Code 001.
ORCID br/documents/33832/2909630/Memento±Fitoterapico/
a80ec477-bb36-4ae0-b1d2-e2461217e06b
Diorge Jônatas Marmitt http://orcid.org/0000-0001- 15. Marmitt DJ, Bitencourt S, Silva AC, Rempel C,
5454-9099 Goettert MI. Medicinal plants used in Brazil public
Shanna Bitencourt http://orcid.org/0000-0002-5854-1550 health system with neuroprotective potential – A
Gustavo Rodrigo da Silva http://orcid.org/0000-0003- systematic review. Bol Latinoam Caribe Plant Med
2669-4365
Aromat. 2018;17(2):84–103.
Claudete Rempel http://orcid.org/0000-0001-8573-0237
16. Marmitt DJ, Bitencourt S, Silva AC, Goettert MI,
Marcia Inês Goettert http://orcid.org/0000-0002-
Rempel C. Scientific production of plant species
3648-5033
included in the Brazilian national list of medicinal
plants of interest to the unified health system
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Nutrition and Cancer

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/hnuc20

RENISUS Plants and Their Potential Antitumor

Diorge Jônatas Marmitt , Shanna Bitencourt , Gustavo Rodrigo da Silva ,

To link to this article: https://doi.org/10.1080/01635581.2020.1810290

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RENISUS Plants and Their Potential Antitumor Effects in Clinical

ABSTRACT ARTICLE HISTORY

Introduction dramatically with age; the overall risk combines with

CONTACT Diorge J^onatas Marmitt [email protected] Laborat

docetaxel (TaxotereV), approved in the 1990s and

peppermint oil (0.05%) flavoring) as an adjunctive

Nutr Cancer. 2014;66(7):1211–9. doi:10.1080/ breast. Am J Clin Nutr. 1998;68(6):1431S–5S. doi:10.

therapy with Ruta graveolens 9c in patients with Med. 2015;21(9):697–702. doi:10.1007/s11655-014-

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