The efficacy of medicinal plant preparations in the alleviation of radiodermatitis in patients with breast cancer: A systematic review of clinical trials.

Radiodermatitis in breast cancer patients varies from mild irritation to life-threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty-five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis.

Preventive and therapeutic use of herbal compounds against doxorubicin induced hepatotoxicity: a comprehensive review.

Doxorubicin (DOX) is associated with numerous acute and chronic dose-related toxicities including hepatotoxicity. This adverse reaction may limit the use of other chemotherapeutic agents with hepatic excretion, and so, its prevention is an important issue. The aim of this study was to conduct a comprehensive review of in vitro, in vivo and human studies regarding the protective effects of synthetic and naturally-occurring compounds against DOX-induced liver injury. The search was conducted in Embase, PubMed, and Scopus databases using the following keywords: "doxorubicin," "Adriamycin," "hepatotoxicity," "liver injury," "liver damage," and "hepatoprotective," and all articles published in English were included without time restriction. Forty eligible studies to the end of May 2022 finally were reviewed. Our results demonstrated that all of these drugs, except acetylsalicylic acid, had considerable hepatoprotective effects against DOX. In addition, none of the studied compounds attenuated the antitumor efficacy of DOX treatment. Silymairn was the only compound which is assessed in human studies and showed promising preventive and therapeutic effects. Altogether, our results demonstrated that most of compounds with antioxidant, anti-apoptosis, and anti-inflammatory properties are efficacious against DOX-induced hepatotoxicity and may be considered as a potential adjuvant agent for prevention of hepatotoxicity in cancer patients, after fully been assessed in well-designed large clinical trials.

Silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions: a comprehensive review of preclinical and clinical data.

PURPOSE: Thus far, silymarin has been examined in several studies for prevention or treatment of various chemotherapy or radiotherapy-induced adverse reactions. In this review, we try to collect all available human, animal, and pre-clinical data in this field. METHODS: The search was done in Scopus, PubMed, Medline, and systematic reviews in the Cochrane database, using the following keywords: "Cancer," "Chemotherapy," "Radiotherapy," "Mucositis," "Nephrotoxicity," "Dermatitis," "Ototoxicity," "Cardiotoxicity," "Nephrotoxicity," "Hepatotoxicity," "Reproductive system," "Silybum marianum," "Milk thistle," and "Silymarin" and "Silybin." We included all relevant in vitro, in vivo, and human studies up to the date of publication. RESULTS: Based on 64 included studies in this review, silymarin is considered a safe and well-tolerated compound, with no known clinical drug interaction. Notably, multiple adverse reactions of chemotherapeutic agents are effectively managed by its antioxidant, anti-apoptotic, anti-inflammatory, and anti-immunomodulatory properties. Clinical trials suggest that oral silymarin may be a promising adjuvant with cancer treatments, particularly against hepatotoxicity (n = 10), nephrotoxicity (n = 3), diarrhea (n = 1), and mucositis (n = 3), whereas its topical formulation can be particularly effective against radiodermatitis (n = 2) and hand-foot syndrome (HFS) (n = 1). CONCLUSION: Further studies are required to determine the optimal dose, duration, and the best formulation of silymarin to prevent and/or manage chemotherapy and radiotherapy-induced complications.

Atorvastatin Efficacy in the Management of Mild to Moderate Hospitalized COVID-19: A Pilot Randomized Triple-blind Placebo- controlled Clinical Trial.

BACKGROUND: Statins are first-line lipid-lowering agents with tolerable adverse reactions, low cost, and high availability worldwide. The potent anti-inflammatory, antioxidant, anti-thrombotic and immunomodulatory effects of statins propose them as an option against COVID-19 infection. OBJECTIVE: In this randomized triple-blind placebo-controlled clinical trial, we have investigated the atorvastatin efficacy in the management of mild to moderate hospitalized COVID-19 patients. METHODS: In this study, 52 mild to moderate hospitalized COVID-19 patients who fulfilled the inclusion criteria were allocated to the treatment group to receive 40 mg atorvastatin orally once daily for two weeks (n=26) or the placebo group (n=26). Patients' symptoms and laboratory investigations were assessed at baseline and during the follow-up period. We also evaluated the duration of hospitalization and supplemental oxygen therapy as endpoints. RESULTS: After 14-day of follow-up, the oxygen saturation (SaO2) was significantly higher, and the serum high sensitivity C-reactive protein (hs-CRP) level was lower in the treatment group compared to the placebo group. Moreover, at the end of the followup in the treatment group, the lymphocyte count was higher, and the duration of symptom resolution was shorter but not significant. Additionally, in the treatment group, the length of supplemental oxygen therapy and hospitalization duration were meaningfully shorter. Our results revealed that the mortality rate was almost twice higher in the placebo group compared to the treatment group, without any significant adverse drug reaction. CONCLUSION: Atorvastatin significantly reduces supplemental oxygen need, hospitalization duration, and serum hs-CRP level in mild to moderate hospitalized COVID-19 patients.

Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: A double-blind placebo-controlled clinical trial.

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration (p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group (p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.

Ethnobotany, Phytochemistry, Traditional and Modern Uses of Actaea racemosa L. (Black cohosh): A Review.

Actaea racemosa (AR) also known as Cimicifuga racemosa, is a perennial plant from Ranunculaceae family which was used as traditional remedies in treatment of various condition like rheumatoid muscular pain, headache, inflammation and dysmenorrhea. Actaea racemosa was basically native to Canada and the Eastern United State. This chapter proposed the ethnopharmacological uses of Actaea racemosa, and its phytochemical properties. Specifically, in this article we focused on use of Actaea racemose for menopausal and post-menopausal symptoms management. Electronic databases including PubMed and Scopus were searched for studies on Actaea racemose and its administration in management of menopausal symptoms. Chem Office software was also used in order to find chemical structures. The key words used as search terms were Cimicifuga racemose, Actaea racemose, Ranunculaceae, Black cohosh, Menopausal symptoms. We have included all relevant animal and human studies up to the date of publication. The analysis on Actaea racemose showed various indications for different plant's extracts. Approximately 131 chemical compounds have been isolated and identified from Actaea racemosa. According to recently studies, the most important chemicals known of the Actaea racemosa are phenolic compounds, chromones, triterpenoids, nitrogen-containing constituents. In addition, in vivo and in vitro studies reported wide range of pharmacological activities for Black cohosh like attenuating menopausal symptoms. Mechanism of action for some ethnomedicinal indications were made clear while some of its activities are not confirmed by pharmacological studies yet. Further investigations on its pharmacological properties are necessary to expand its clinical effective use. Also, additional large clinical trials are recommended for clarifying the effect of Black cohosh.

Ethnobotany, Phytochemistry and Pharmacological Features of Centella asiatica: A Comprehensive Review.

Centella asiatica (CA) or Gotu cola is an herbal plant from the Apiaceae family with a long history of usage in different traditional medicines. It has long been used for the treatment of various ailments such as central nervous system (CNS), skin and gastrointestinal disorders especially in the Southeast Asia. This chapter focused on the phytochemical constituent and pharmacological activities of CA based on preclinical and clinical studies. Additionally, botanical description and distribution, traditional uses, interactions, and safety issues are reviewed. Electronic databases of Google Scholar, Scopus, PubMed, and Web of Science were searched to obtain relevant studies on the pharmacological activities of CA. Approximately, 124 chemical compounds including triterpenoids, polyphenolic compounds, and essential oils have been isolated and identified from CA. Ethnomedicinal applications of CA mostly include treatment of gastrointestinal diseases, wounds, nervous system disorders, circulatory diseases, skin problems, respiratory ailments, diabetes and sleep disorders in various ethnobotanical practices. Pharmacological studies revealed a wide range of beneficial effects of CA on CNS, cardiovascular, lung, liver, kidney, gastrointestinal, skin, and endocrine system. Among them, neuroprotective activity, wound healing and treatment of venous insufficiency, as well as antidiabetic activity seem to be more frequently reported. At the moment, considering various health benefits of CA, it is marketed as an oral supplement as well as a topical ingredient in some cosmetic products. Additional preclinical studies and particularly randomized controlled trials are needed to clarify the therapeutic roles of CA.

Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial.

Curcumin is proposed as a potential treatment option for coronavirus disease-19 (COVID-19) by inhibiting the virus entrance, encapsulation and replication, and modulating various cellular signaling pathways. In this open-label nonrandomized clinical trial, efficacy of nano-curcumin oral formulation has been evaluated in hospitalized patients with mild-moderate COVID-19. Forty-one patients who fulfilled the inclusion criteria were allocated to nano-curcumin (n = 21) group (Sinacurcumin soft gel, contains 40 mg curcuminoids as nanomicelles, two capsules twice a day) or control (n = 20) group, for 2 weeks. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period. Most of symptoms including fever and chills, tachypnea, myalgia, and cough resolved significantly faster in curcumin group. Moreover, SaO2 was significantly higher in treatment group after 2, 4, 7, and 14 days of follow-up and lymphocyte count after 7 and 14 days. Duration of supplemental O2 use and hospitalization was also meaningfully shorter in treatment group. It is also noteworthy to mention that no patient in treatment group experienced deterioration of infection during follow-up period, but it occurred in 40% of control group. Oral curcumin nano-formulation can significantly improve recovery time in hospitalized COVID-19 patients. Further randomized placebo controlled trials with larger sample size are recommended.

Curcumin as a preventive or therapeutic measure for chemotherapy and radiotherapy induced adverse reaction: A comprehensive review.

Curcumin has attracted much attention for medicinal purposes in wide range of illnesses including cancer. In some studies, its efficacy is evaluated against chemotherapy and radiotherapy induced adverse reaction and also as adjuvant to cancer treatment. Here we have tried to present a comprehensive review on protective and therapeutic effect of curcumin against these side effects. METHOD: The data were collected by searching Scopus, PubMed, Medline, and Cochrane database systematic reviews, using key words "nephrotoxicity", "cardiotoxicity", "genotoxicity", "ototoxicity", "hepatotoxicity", "reproductive toxicity", "myelosuppression", "pulmonary toxicity", "radiotherapy induced side effect" with "turmeric" and "curcumin". Although curcumin has low bioavailability, it has shown brilliant profile on prevention and management of chemotherapy and radiotherapy induced adverse reactions, particularly based on in vitro and in vivo studies and limited number of human studies on radiotherapy adverse reactions. Antioxidant and anti-inflammatory properties of the curcumin are the main proposed mechanism of action for management and prevention of adverse reactions. One of the major points regarding the protective effect of curcumin is its wide tolerable therapeutic range of dose with minimal side effects. Furthermore, new nano-formulations help to improve the bioavailability, increase in efficacy and lower the adverse effects. In conclusion, based on the present knowledge, curcumin has significant supportive potential in patients receiving chemotherapy or radiotherapy and may be suggested as adjutant with cancer treatments. Further well-designed human studies are recommended.

Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial.

Radiation-induced dermatitis is one of the most common side effects of radiotherapy. Silymarin, a flavonoid extracted from the Silybum marianum, exhibits antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the efficacy of silymarin gel in prevention of radiodermatitis in patients with breast cancer. During this randomized, double-blinded, placebo-controlled clinical trial, the preventive effect of silymarin 1% gel was assessed in comparison with placebo, on radiodermatitis occurrence. Forty patients randomly received silymarin gel or placebo formulation on chest wall skin following modified radical mastectomy, once daily starting at the first day of radiotherapy for 5 weeks. Radiodermatitis severity was assessed weekly based on Radiation Therapy Oncology Group (RTOG) and National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE) criteria radiodermatits grading scale for 5 weeks. The median NCI-CTCAE and RTOG scores were significantly lower in silymarin group at the end of the third to fifth weeks (p value < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay in radiodermatitis development and progression in silymarin group. Prophylactic administration of silymarin gel could significantly reduce the severity of radiodermatitis and delay its occurrence after 5 weeks of application.

Topical Silymarin Administration for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Hand-foot syndrome (HFS) is a frequent dose-limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine-induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9th week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine-induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Mucositis is a frequent severe complication of radiation therapy in patient with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluate silymarin efficacy in prevention of radiotherapy induced mucositis in patients with head and neck cancer, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy for 6 weeks, on oral mucositis occurrence was assessed. Twenty-seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization and National Cancer Institute-Common Terminology Criteria oral mucositis grading scale scores were recorded at baseline and weekly during these 6 weeks. The median World Health Organization and National Cancer Institute Common Terminology Criteria scores were significantly lower in silymarin group at the end of the first to sixth week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay for mucositis development and progression in silymarin group. Prophylactic administration of conventional form of silymarin tablets could significantly reduce the severity of radiotherapy induced mucositis and delay its occurrence in patients with head and neck cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Carnitine and sepsis: a review of an old clinical dilemma.

PURPOSE: The precise role of carnitine as the key regulator of lipid metabolism in sepsis is unclear. In this review, available experimental as well as clinical evidences regarding the probable beneficial effects of carnitine in sepsis were evaluated. METHOD: A comprehensive literature search was performed in the related medical databases. Related experimental and clinical studies were included. RESULTS AND CONCLUSION: The plasma and tissue level of carnitine or its derivatives in septic condition is variable and inconclusive. Survival and outcomes are considered in only few studies. Despite its favorable safety profile, due to limited clinical evidence, it seems reasonable not to currently consider carnitine as a mandatory and beneficial supplement under septic conditions. Further well-designed, standard clinical trials are warranted in this regards.

Prevention of vancomycin induced nephrotoxicity: a review of preclinical data.

PURPOSE: Several strategies have been proposed for the prevention of vancomycin-induced nephrotoxicity. Here, we review available evidence supporting the respective strategies. METHOD: Data were collected by searching the Scopus, PubMed, and Medline databases and the Cochrane database of systematic reviews. The key words used as search terms were "vancomycin," "nephrotoxicity", "renal failure," "renal damage," "nephroprotective," "renoprotective", and "prevention." Prospective or retrospective observational animal studies that evaluated the effects of a modality for the prevention of vancomycin-induced nephrotoxicity was included. RESULTS AND CONCLUSION: Animal studies show beneficial effects of various antioxidants, such as erdosteine, vitamin E, vitamin C, N-acetylcysteine, caffeic acid phenethyl ester, and erythropoietin, in the prevention of vancomycin-induced nephrotoxicity. However, before these agents can be used in clinical practice, their potential benefits must be confirmed in future randomized controlled human studies.