Showing papers in "Phytotherapy Research in 2020"
TL;DR: A comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of aloe‐emodin reported to date is provided with an emphasis on its biological properties and mechanisms of action.
Abstract: Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long-term use Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action Copyright © 2016 John Wiley & Sons, Ltd
335 citations
TL;DR: Some of the potential effects of curcumin such as inhibiting the entry of virus to the cell, inhibiting encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways are reviewed.
Abstract: Coronavirus disease 2019 (COVID-19) outbreak is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with considerable mortality worldwide. The main clinical manifestation of COVID-19 is the presence of respiratory symptoms, but some patients develop severe cardiovascular and renal complications. There is an urgency to understand the mechanism by which this virus causes complications so as to develop treatment options. Curcumin, a natural polyphenolic compound, could be a potential treatment option for patients with coronavirus disease. In this study, we review some of the potential effects of curcumin such as inhibiting the entry of virus to the cell, inhibiting encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways. This review provides a basis for further research and development of clinical applications of curcumin for the treatment of newly emerged SARS-CoV-2.
226 citations
TL;DR: A good number of natural products with anti‐corona virus activity are the major constituents of some common dietary supplements, which can be exploited to improve the immunity of the general population in certain epidemics.
Abstract: Several corona viral infections have created serious threats in the last couple of decades claiming the death of thousands of human beings. Recently, corona viral epidemic raised the issue of developing effective antiviral agents at the earliest to prevent further losses. Natural products have always played a crucial role in drug development process against various diseases, which resulted in screening of such agents to combat emergent mutants of corona virus. This review focuses on those natural compounds that showed promising results against corona viruses. Although inhibition of viral replication is often considered as a general mechanism for antiviral activity of most of the natural products, studies have shown that some natural products can interact with key viral proteins that are associated with virulence. In this context, some of the natural products have antiviral activity in the nanomolar concentration (e.g., lycorine, homoharringtonine, silvestrol, ouabain, tylophorine, and 7-methoxycryptopleurine) and could be leads for further drug development on their own or as a template for drug design. In addition, a good number of natural products with anti-corona virus activity are the major constituents of some common dietary supplements, which can be exploited to improve the immunity of the general population in certain epidemics.
158 citations
TL;DR: It is concluded that naringenin may be a promising treatment strategy against COVID‐19, a novel flu‐like coronavirus recognized by World Health Organization at the end of 2019.
Abstract: At the end of 2019, a novel flu-like coronavirus named COVID-19 (coronavirus disease 2019) was recognized by World Health Organization. No specific treatments exist for COVID-19 at this time. New evidence suggests that therapeutic options focusing on antiviral agents may alleviate COVID-19 symptoms as well as those that lead to the decrease in the inflammatory responses. Flavonoids, as phenolic compounds, have attracted considerable attention due to their various biological properties. In this review, the promising effects and possible mechanisms of action of naringenin, a citrus-derived flavonoid, against COVID-19 were discussed. We searched PubMed/Medline, Science direct, Scopus, and Google Scholar databases up to March 2020 using the definitive keywords. The evidence reviewed here indicates that naringenin might exert therapeutic effects against COVID-19 through the inhibition of COVID-19 main protease, 3-chymotrypsin-like protease (3CLpro), and reduction of angiotensin converting enzyme receptors activity. One of the other mechanisms by which naringenin might exert therapeutic effects against COVID-19 is, at least partly, by attenuating inflammatory responses. The antiviral activity of the flavanone naringenin against some viruses has also been reported. On the whole, the favorable effects of naringenin lead to a conclusion that naringenin may be a promising treatment strategy against COVID-19.
124 citations
TL;DR: Apigenin treatment leads to significant downregulation of matrix metallopeptidases-2, -9, Snail, and Slug, suppressing invasion and apigenin-mediated treatment significantly reduces pluripotency marker Oct3/4 protein expression which might be associated with the down regulation of PI3K/Akt/NF-κB signaling.
Abstract: Apigenin is an edible plant-derived flavonoid that has been reported as an anticancer agent in several experimental and biological studies. It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways. Apigenin induces apoptosis by the activation of extrinsic caspase-dependent pathway by upregulating the mRNA expressions of caspase-3, caspase-8, and TNF-α. It induces intrinsic apoptosis pathway as evidenced by the induction of cytochrome c, Bax, and caspase-3, while caspase-8, TNF-α, and B-cell lymphoma 2 levels remained unchanged in human prostate cancer PC-3 cells. Apigenin treatment leads to significant downregulation of matrix metallopeptidases-2, -9, Snail, and Slug, suppressing invasion. The expressions of NF-κB p105/p50, PI3K, Akt, and the phosphorylation of p-Akt decreases after treatment with apigenin. However, apigenin-mediated treatment significantly reduces pluripotency marker Oct3/4 protein expression which might be associated with the downregulation of PI3K/Akt/NF-κB signaling.
100 citations
TL;DR: An extensive overview of the traditional medicinal, phytochemical and multiple biological activities of this “Peppermint” is provided.
Abstract: Peppermint (Mentha × piperita L) is a perennial, glabrous and strongly scented herb belongs to the family Lamiaceae. It is cultivated in a temperate region of Europe, Asia, United States, India and Mediterranean countries due to their commercial value and distinct aroma. In addition to traditional food flavouring uses, M. × piperita is well recognized for their traditional use to treat fever, cold, digestive, anti-viral, anti-fungal and oral mucosa and throat inflammation. The scientific studies provide awareness on the use of M. × piperita for biological effects such as anti-oxidant, anti-microbial, anti-viral, anti-inflammatory, biopesticidal, larvicidal, anticancer, radioprotective effect, genotoxicity and anti-diabetic activity have been ascribed. A wide spectrum of bioactive phytochemicals such as flavonoids, phenolics lignans and stilbenes and essential oils are expected to be responsible for the aroma effects. In this sense, this present review provides an extensive overview of the traditional medicinal, phytochemical and multiple biological activities of this "Peppermint."
93 citations
TL;DR: The aim of this work is to summarize the updated evidence for antiviral activity of different plants and their isolated bioactive compounds, evaluating also the potential interactions, which can occur in cotreatment with conventional antiviral drugs.
Abstract: Viral infections represent one of the main causes of disease worldwide, especially today due to the increase of migration, global travel, and urbanization. The several side effects of the conventional drugs and the growing phenomenon of resistance have led researchers to turn to the plant kingdom as a source of potential new antiviral drugs. The aim of this work is to summarize the updated evidence for antiviral activity of different plants and their isolated bioactive compounds, evaluating also the potential interactions, which can occur in cotreatment with conventional antiviral drugs. The plant complexes have proved to be usually more active than their most abundant isolated compounds by hypothesizing synergistic mechanisms. In addition to cellular and molecular investigations, molecular docking studies have proved essential in highlighting the interaction mechanisms of bioactive compounds with target molecules. However, the use of nonstandardized extracts, or too high concentrations in vitro, which do not reproduce their bioavailability in vivo, are often limiting factors. Moreover, the lack of studies concerning the safety profile of plant extracts and their isolated compounds, alone or in combination with conventional antiviral drugs, is the most worrying aspect. In light of this, further studies are needed to validate their possible therapeutic use.
87 citations
TL;DR: Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredients were found to be effective in the management of obesity and metabolic syndrome.
Abstract: Obesity is a medical situation in which excess body fat has gathered because of imbalance between energy intake and energy expenditure. In spite of the fact that the variety of studies are available for obesity treatment and management, its "globesity" still remains a big challenge all over the world. The current systematic review and meta-analysis aimed to evaluate the efficacy, safety, and mechanisms of effective herbal medicines in the management and treatment of obesity and metabolic syndrome in human. We systematically searched all relevant clinical trials via Web of Science, Scopus, PubMed, and the Cochrane database to assess the effects of raw or refined products derived from plants or parts of plants on obesity and metabolic syndrome in overweight and obesity adult subjects. All studies conducted by the end of May 2019 were considered in the systematic review. Data were extracted independently by two experts. The quality assessment was assessed using Consolidated Standards of Reporting Trials checklist. The main outcomes were anthropometric indices and metabolic syndrome components. Pooled effect of herbal medicines on obesity and metabolic syndrome were presented as standardized mean difference (SMD) and 95% confidence interval (CI). A total of 279 relevant clinical trials were included. Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredients were found to be effective in the management of obesity and metabolic syndrome. In addition, C. fimbriata, flaxseed, spinach, and fenugreek were able to reduce appetite. Meta-analysis showed that intake of green tea resulted in a significant improvement in weight ([SMD]: -0.75 [-1.18, -0.319]), body mass index ([SMD]: -1.2 [-1.82, -0.57]), waist circumference ([SMD]: -1.71 [-2.66, -0.77]), hip circumference ([SMD]: -0.42 [-1.02, -0.19]), and total cholesterol, ([SMD]: -0.43 [-0.77, -0.09]). In addition, the intake of P. vulgaris and N. sativa resulted in a significant improvement in weight ([SMD]: -0.88, 95 % CI: [-1.13, -0.63]) and triglyceride ([SMD]: -1.67, 95 % CI: [-2.54, -0.79]), respectively. High quality trials are still needed to firmly establish the clinical efficacy of the plants in obesity and metabolic syndrome.
80 citations
TL;DR: A range of in vitro and in vivo studies have been critically discussed to explore the therapeutic viability and pharmaceutical significance of the nano-formulated delivery systems to elevate the anti-bacterial activities of curcumin and its derivatives.
Abstract: Curcumin has been used in numerous anti-microbial research because of its low side effects and extensive traditional applications. Despite having a wide range of effects, the intrinsic physicochemical characteristics such as low bioavailability, poor water solubility, photodegradation, chemical instability, short half-life and fast metabolism of curcumin derivatives limit their pharmaceutical importance. To overcome these drawbacks and improve the therapeutic ability of curcuminoids, novel approaches have been attempted recently. Nanoparticulate drug delivery systems can increase the efficiency of curcumin in several diseases, especially infectious diseases. These innovative strategies include polymeric nanoparticles, hydrogels, nanoemulsion, nanocomposite, nanofibers, liposome, nanostructured lipid carriers (NLCs), polymeric micelles, quantum dots, polymeric blend films and nanomaterial-based combination of curcumin with other anti-bacterial agents. Integration of curcumin in these delivery systems has displayed to improve their solubility, bioavailability, transmembrane permeability, prolong plasma half-life, long-term stability, target-specific delivery and upgraded the therapeutic effects. In this review paper, a range of in vitro and in vivo studies have been critically discussed to explore the therapeutic viability and pharmaceutical significance of the nano-formulated delivery systems to elevate the anti-bacterial activities of curcumin and its derivatives.
77 citations
TL;DR: A comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms is obtained.
Abstract: Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T-cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.
74 citations
TL;DR: The aim of this study was to evaluate the effect of curcumin on improvement of the disease activity in ulcerative colitis.
Abstract: Background and aims Curcumin has anti-inflammatory properties. The aim of this study was to evaluate the effect of curcumin on improvement of the disease activity in ulcerative colitis (UC). Methods In this randomized double-blind clinical trial, 70 patients with mild-to-moderate UC were randomly assigned to curcumin (1,500 mg/day) or placebo intake for 8 weeks. Disease clinical activity, quality of life, serum levels of tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) values, and complete blood count were measured. Results Changes in Simple Clinical Colitis Activity Index score were significantly higher in the curcumin than the placebo group (-5.9 ± 2.08 vs. -2.1 ± 2.6; p = .001). The scores of Inflammatory Bowel Disease Questionnaire-9 and quality of life were significantly higher in the intervention group compared to the control group (p = .006). Furthermore, the curcumin supplementation reduced the serum hs-CRP concentration (-6.3 ± 13.6 vs. 3.7 ± 11.6 μg/ml; p = .01) and ESR levels significantly (-1.6 ± 2.7 vs. -0.09 ± 2.4 mm/hr; p = .02) in comparison with the control group. No significant changes were observed in the TNF-α levels of both groups. Conclusions Consumption of the curcumin supplement, along with drug therapy, is associated with significant improvement of the clinical outcomes, quality of life, hs-CRP, and ESR in patients with mild-to-moderate UC.
TL;DR: The present review was designed to report important functional food plants with immunomodulatory and anti‐viral properties that might reduce the risk of COVID‐19 and initiate a rapid recovery in cases of SARS‐CoV‐2 infection.
Abstract: The recent and ongoing outbreak of coronavirus disease (COVID-19) is a huge global challenge. The outbreak, which first occurred in Wuhan City, Hubei Province, China and then rapidly spread to other provinces and to more than 200 countries abroad, has been declared a global pandemic by the World Health Organization. Those with compromised immune systems and/or existing respiratory, metabolic or cardiac problems are more susceptible to the infection and are at higher risk of serious illness or even death. The present review was designed to report important functional food plants with immunomodulatory and anti-viral properties. Data on medicinal food plants were retrieved and downloaded from English-language journals using online search engines. The functional food plants herein documented might not only enhance the immune system and cure respiratory tract infections but can also greatly impact the overall health of the general public. As many people in the world are now confined to their homes, inclusion of these easily accessible plants in the daily diet may help to strengthen the immune system and guard against infection by SARS-CoV-2. This might reduce the risk of COVID-19 and initiate a rapid recovery in cases of SARS-CoV-2 infection.
TL;DR: Curcumin is capable of crossing the blood-brain barrier, and thus it may protect the neurons from oxidative stress and inflammation, and it is possible to use it in the protection of liver and spleen against oxidative and inflammatory injury.
Abstract: Recently, many studies have been conducted trying to explain the molecular mechanism of curcumin action in various pathological states of the cell and the organism. Curcumin is considered to play a role in the regulation of T-lymphocytes function in the lymphoid tissue of the large intestine, apoptosis of the human papilloma and the activity of the 26S proteasome, and p53 level. Research works have shown that curcumin in tumor can regulate reactive oxygen species (ROS) and cytosolic calcium ion level as well as affect other signaling molecules [nuclear factor kappa B (NF-KB), cytokines] triggering endoplasmic reticulum and mitochondrial stress, and thus contributing to death of cancer cells. Curcumin can also arrest of the cell cycle in the G2/M phase leading to apoptosis and/or reduction in cancer cells proliferation. Moreover, curcumin is capable of crossing the blood-brain barrier, and thus it may protect the neurons from oxidative stress and inflammation. Finally, curcumin may play a role in cardiological protection and it is possible to use it in the protection of liver and spleen against oxidative and inflammatory injury. Among signaling pathways regulated by curcumin, the most important seem to be those related with regulation of oxidative stress and inhibition of NF-кB activity.
TL;DR: This study was undertaken to review the pharmacological effects, pharmacokinetic properties as well as toxicity and pharmaceutical applications of GA.
Abstract: Beneficial therapeutic effects of phenolic acids have been proven in various research projects including in vivo and in vitro studies. Gentisic acid (GA) is a phenolic acid that has been associated with useful effects on human health, such as antiinflammatory, antigenotoxic, hepatoprotective, neuroprotective, antimicrobial, and especially antioxidant activities. It is an important metabolite of aspirin and also widely distributed in plants as a secondary plant product such as Gentiana spp., Citrus spp., Vitis vinifera, Pterocarpus santalinus, Helianthus tuberosus, Hibiscus rosa-sinensis, Olea europaea, and Sesamum indicum and in fruits such as avocados, batoko plum, kiwi fruits, apple, bitter melon, black berries, pears, and some mushrooms. This study was undertaken to review the pharmacological effects, pharmacokinetic properties as well as toxicity and pharmaceutical applications of GA.
TL;DR: A new generation of bioformulations based on microbial metabolites and living consortia responsible for the desired beneficial effects on crops may overcome the difficulties associated with the use of a single living microbial strain.
Abstract: Selected microbial strains used as active ingredients of biopesticides for agricultural management practices (eg, IPM, Integrated Pest Management) are known for their ability to control phytopathogens, promote plant growth, and/or induce disease resistance Microbes belonging to the Trichoderma genus are considered as an appropriate example of beneficial microbes and are model organisms to study plant-microbe interactions Several Trichoderma strains are marketed as biocontrol agents and are known to increase plant growth, stress tolerance, and nutrient availability These effects have sometimes been related to the production of effector metabolites that beneficial microbes produce during the interaction with plant and other microbes Secondary metabolites (SMs) comprise different classes of natural compounds with low molecular weight and having numerous biological roles, especially in the interactions among organisms Metabolomic analysis of the interactions between plants, phytopathogens, and beneficial fungi aided in the identification of several bioactive fungal SMs that positively affect plant metabolism Some of these compounds showed direct activity against phytopathogens, but also increased disease resistance by triggering the plant defence system, and/or enhanced vegetative growth A new generation of bioformulations based on microbial metabolites and living consortia responsible for the desired beneficial effects on crops may overcome the difficulties associated with the use of a single living microbial strain
TL;DR: This review aimed to integrate the information on the customary attributes of the plant star anise with a specific prominence on its antiviral properties and the phytochemical constituents along with its clinical aptness.
Abstract: Medicinal herbs are one of the imperative sources of drugs all over the world. Star anise (Illicium verum), an evergreen, medium-sized tree with star-shaped fruit, is an important herb with wide distribution throughout southwestern parts of the Asian continent. Besides its use as spice in culinary, star anise is one of the vital ingredients of the Chinese medicinal herbs and is widely known for its antiviral effects. It is also the source of the precursor molecule, shikimic acid, which is used in the manufacture of oseltamivir (Tamiflu®), an antiviral medication for influenza A and influenza B. Besides, several other molecules with numerous biological benefits including the antiviral effects have been reported from the same plant. Except the antiviral potential, star anise possesses a number of other potentials such as antioxidant, antimicrobial, antifungal, anthelmintic, insecticidal, secretolytic, antinociceptive, anti-inflammatory, gastroprotective, sedative properties, expectorant and spasmolytic, and estrogenic effects. This review aimed to integrate the information on the customary attributes of the plant star anise with a specific prominence on its antiviral properties and the phytochemical constituents along with its clinical aptness.
TL;DR: Natural products like ginger, turmeric, garlic, onion, cinnamon, lemon, neem, basil, and black pepper have been scientifically proven to have therapeutic benefits against acute respiratory tract infections including pulmonary fibrosis, diffuse alveolar damage, pneumonia, and acute respiratory distress syndrome, all of which are symptoms associated with COVID‐19 infection.
Abstract: Coronavirus disease (COVID-19) caused by the novel coronavirus (SARS-CoV-2) has rapidly spread across the globe affecting 213 countries or territories with greater than six million confirmed cases and about 0.37 million deaths, with World Health Organization categorizing it as a pandemic. Infected patients present with fever, cough, shortness of breath, and critical cases show acute respiratory infection and multiple organ failure. Likelihood of these severe indications is further enhanced by age as well as underlying comorbidities such as diabetes, cardiovascular, or thoracic problems, as well as due to an immunocompromised state. Currently, curative drugs or vaccines are lacking, and the standard of care is limited to symptom management. Natural products like ginger, turmeric, garlic, onion, cinnamon, lemon, neem, basil, and black pepper have been scientifically proven to have therapeutic benefits against acute respiratory tract infections including pulmonary fibrosis, diffuse alveolar damage, pneumonia, and acute respiratory distress syndrome, as well as associated septic shock, lung and kidney injury, all of which are symptoms associated with COVID-19 infection. This review highlights the potential of these natural products to serve as home-based, inexpensive, easily accessible, prophylactic agents against COVID-19.
TL;DR: This review summarizes findings in the literature and shows the therapeutic potential of red beetroot and its active compounds (betalains) as promising alternatives for supplemental therapies in multiple diseases.
Abstract: Over the past few years, the use of natural substances as protective or therapeutic agents has gained much attention worldwide. Recent modern studies have shown a variety of health benefits for red beetroot and its active compounds betalains (also betanin) such as antioxidative, anti-inflammation, anticancer, blood pressure and lipid lowering, also antidiabetic and anti-obesity effects. Betanin, the main component of the red beetroot, is a betalain glycosidic pigment, which is used as a food additive. This review summarizes findings in the literature and shows the therapeutic potential of red beetroot and its active compounds (betalains) as promising alternatives for supplemental therapies in multiple diseases.
TL;DR: How kaempferol modulates autophagy and ER stress in noncancer and cancer cells to expand the knowledge of new pharmacological compounds for the treatment of associated diseases is discussed.
Abstract: Regulated cell death (RCD) guarantees to preserve organismal homeostasis. Apoptosis and autophagy are two major arms of RCD, while endoplasmic reticulum (ER) as a crucial organelle involved in proteostasis, promotes cells toward autophagy and apoptosis. Alteration in ER stress and autophagy machinery is responsible for a great number of diseases. Therefore, targeting those pathways appears to be beneficial in the treatment of relevant diseases. Meantime, among the traditional herb medicine, kaempferol as a flavonoid seems to be promising to modulate ER stress and autophagy and exhibits protective effects on malfunctioning cells. There are some reports indicating the capability of kaempferol in affecting autophagy and ER stress. In brief, kaempferol modulates autophagy in noncancerous cells to protect cells against malfunction, while it induces cell mortality derived from autophagy through the elevation of p-AMP-activated protein kinase, light chain-3-II, autophagy-related geness, and Beclin-1 in cancer cells. Noteworthy, kaempferol enhances cell survival through C/EBP homologous protein (CHOP) suppression and GRP78 increment in noncancerous cells, while it enhances cell mortality through the induction of unfolding protein response and CHOP increment in cancer cells. In this review, we discuss how kaempferol modulates autophagy and ER stress in noncancer and cancer cells to expand our knowledge of new pharmacological compounds for the treatment of associated diseases.
TL;DR: A new mechanism of quercetin improving AKI‐induced kidney inflammation and injury is clarified, which provides a new drug option for the clinical treatment of AKI.
Abstract: Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF-κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL-1β, IL-6, and TNF-α in LPS-induced bone marrow-derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF-κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL-1β, IL-6, and TNF-α in cisplatin-induced AKI model. Furthermore, quercetin down-regulated protein levels of Mincle, phosphorylated Syk and NF-κB in kidney macrophages of AKI, as well as inhibited M1, up-regulated M2 macrophage activity. Notably, the down-regulation of LPS-induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI-induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.
TL;DR: The aim of this article is to review the available scientific information regarding the traditional uses, bioactive chemical constituents and the pharmacological activities of T. chebula.
Abstract: Fruits of Terminalia chebula Retz. (Combretaceae) are widely used as crude drugs in various traditional medicine systems. The aim of this article is to review the available scientific information regarding the traditional uses, bioactive chemical constituents and the pharmacological activities of T. chebula. Numerous researches conducted on T. chebula have confirmed the presence of wide range of the phytochemicals such as flavonoids, tannins, phenolic acids and other bioactive compounds. T. chebula is also widely studied regarding its pharmacological activities such as antioxidant, hepatoprotective, neuroprotective, cytotoxic, antidiabetic, anti-inflammatory activities among others. However, more in vivo and clinical studies for mechanism-based pharmacological evaluation should be conducted in future to provide stronger scientific evidences for their traditional uses.
TL;DR: The use of green tea can be combined with a balanced and healthy diet and regular physical exercise in the management of obese patients and the results of present meta‐analysis support the use of GT for the improvement of obesity indices.
Abstract: The effects of green tea (GT) in obese subjects have been evaluated in different studies, but no consensus has been obtained due to the heterogeneity of the results. The dosage, the type of extract, and the duration of the intervention are the main contributors to the heterogeneity of the results. Therefore, the present systematic review and meta-analysis aimed to evaluate the efficacy and dose-response relationship of GT. Several databases were searched from inception to September 2019 to identify clinical trials that examined the influence of GT supplements on obesity indices in humans. Combined results using the random-effects model indicated that body weight (WMD: -1.78 kg, 95% CI: -2.80, -0.75, p = .001) and body mass index (BMI) (WMD: -0.65 kg/m2 , 95% CI: -1.04, -0.25, p = .001) did change significantly following GT administration. The reduction in waist circumference (WC) after GT consumption was significant in subjects in trials employing GT ≥800 mg/day (WMD: -2.06 cm) and with a treatment duration <12 weeks (WMD: -2.39 cm). Following the dose-response evaluation, GT intake did alter body weight, with a more important reduction when the GT dosage was <500 mg/day and the treatment duration was of 12 weeks. The results of present meta-analysis study support the use of GT for the improvement of obesity indices. Thus, we suggest that the use of GT can be combined with a balanced and healthy diet and regular physical exercise in the management of obese patients.
TL;DR: Curcumin is able to enhance the level of anti-inflammatory cytokines and improve inflammatory disorders such as colitis by targeting STAT signaling pathway, and studies show that inhibition of JAK/STAT pathway by curcuming is involved in reduced migration and invasion of cancer cells.
Abstract: Curcumin is a naturally occurring nutraceutical compound with a number of therapeutic and biological activities such as antioxidant, anti-inflammatory, anti-diabetic, antitumor, and cardioprotective. This plant-derived chemical has demonstrated great potential in targeting various signaling pathways to exert its protective effects. Signal transducers and activator of transcription (STAT) is one of the molecular pathways involved in a variety of biological processes such as cell proliferation and cell apoptosis. Accumulating data demonstrates that the STAT pathway is an important target in treatment of a number of disorders, particularly cancer. Curcumin is capable of affecting STAT signaling pathway in induction of its therapeutic impacts. Curcumin is able to enhance the level of anti-inflammatory cytokines and improve inflammatory disorders such as colitis by targeting STAT signaling pathway. Furthermore, studies show that inhibition of JAK/STAT pathway by curcumin is involved in reduced migration and invasion of cancer cells. Curcumin normalizes the expression of JAK/STAT signaling pathway to exert anti-diabetic, renoprotective, and neuroprotective impacts. At the present review, we provide a comprehensive discussion about the effect of curcumin on JAK/STAT signaling pathway to direct further studies in this field.
TL;DR: Flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues than for solid tumors, and because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promotepositive outcomes for cancer patients.
Abstract: Flavonoids have been proposed as potential chemotherapeutic agents because they are toxic against cancer cells but not harmful to healthy cells. This systematic review analyzed flavonoid effectiveness in human cancer chemotherapy. Overall, 22 phase II and 1 phase III clinical trials (PubMed, Scopus, and Web of Science) that used flavonoids as a single agent or combined with other therapeutics against hematopoietic/lymphoid or solid cancer published by January 2019 were selected for analysis. Flavopiridol was the most commonly used flavonoid (at a dose of 50-mg/m2 IV) for all tumor types. Aside from the relatively low rate of complete response (CR) or partial response (PR) with any administration protocol, flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues (140 patients with CR and 88 with PR among 615 patients in 11 trials) than for solid tumors (4 patients with CR and 21 with PR among 525 patients in 12 trials). However, because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promote positive outcomes for cancer patients.
TL;DR: Empirical observations coupled with sound basic evidence may provide clues in the search for strategies to fight this pandemic, and countries in Southeast Asia, which are the largest producers and consumers of curcumin, have shown a very low number of deaths attributed to SARS-CoV-2 infections.
Abstract: Dear Editor, Although a worldwide phenomenon, severe acute respiratory syndrome (SARS) by the new coronavirus (SARS-CoV-2) infection is apparently less severe in some parts of the world with some countries presenting a surprisingly low death toll (https://coronavirus.jhu.edu/ map.html; in 6 May 08:53 a.m.). No one would argue that a specific treatment with a well-defined mechanism would be the best approach to fight this pandemic. However, given the urgency, clinical trials based on pragmatism, using the prima non nocere principle, may be justified. Epidemiological observations coupled with sound basic evidence may thus provide clues in the search for such strategies. Turmeric (Indian saffron), a much-appreciated spice, has India as by far the greater producer and consumer, together with Pakistan, Malaysia, Bangladesh, Sri Lanka, Taiwan, China, Burma (Myanmar), and Indonesia (http://www.fao.org/fileadmin/user_upload/inpho/docs/Post_Har vest_Compendium_-_Turmeric.pdf downloaded in 21 March 2020). Curcuma or curcuminoids isolated from Turmeric have long been reported to have antiinflammatory and immunomodulatory activity. Due to its low bioavailability, alternatives to improve turmeric absorption have been developed. Although edible consumption may provide health benefits, pharmaceutical preparations increase curcumin absorption thus allowing pharmacodynamic and pharmacokinetic data on the serum levels of curcuminoids (Aggarwal, Gupta, & Sung, 2013). A world map of the new coronavirus disease (COVID-19) reveals that countries in Southeast Asia, which are the largest producers and consumers of curcumin, have shown a very low number of deaths attributed to SARS-CoV-2 infections. Our attention was driven to the death toll from the COVID-19 because the number of infected people is likely underestimated. We excluded Taiwan from our analysis given the apparently efficient strict rules for isolation implemented there as well as its presumed disposal of adequate health facilities. As of 23 April, the total death toll from COVID-19 reported in India, Indonesia, Pakistan, Bangladesh, Malaysia, Sri Lanka, and Burma was 3.424, being 1,695, 895, 526, 186, 107, 9, and 6 in each country, respectively (https://coronavirus.jhu.edu/map.html downloaded in 6 May, 08:53 a.m.). Let us not forget that the sum of the population in those countries represents over one quarter of the world population. At the same time, it was interesting to note that Iran has a COVID-19 death toll of 6.418 as of 6 May. Curiously, Iran, once a greater consumer of Turmeric, has experienced a shortage of this product in the last years due to economic sanctions (https://economictimes.indiatimes.com/ news/economy/foreign-trade/turmeric-exports-hit-by-us-sanctionsagainst-iran/articleshow/70446034.cms?from=mdr; downloaded in 6 May 2020, 08:53 a.m.). Community isolation has been hard to implement in those Southeast Asian countries which, like Iran, do also experience a shortage of health facilities and supplies to face this epidemic. We were also impressed by the great difference between the number of deaths attributed to COVID-19 in those heavy curcuminconsuming countries and those in some western European countries. We should also consider that some of those European countries have implemented severe rules restricting social activities as an attempt to mitigate disease spreading, in addition to having far better health systems available. We started this observation in the early days of March 2020, but the death toll is persistently very low in those Southeast Asian countries, thus reinforcing its relevance. There are a lot of possible confounders impacting this epidemiological observation. Why would more people die from COVID-19 in such wealthy countries and why would Iranians be so heavily penalised? Considering the excellence of health systems in most western European countries, we may assume they provide more accurate data on diagnostic testing, which are lacking in those Southeast Asian countries as well as in Iran. Thus, counting the number of deaths attributed to COVID-19 might better illustrate the burden of this disease across different populations. Although ethnicity could play a role, the large variability across those heavy curcumin consumers both within and between countries make it unlikely to be relevant. The vast geographical area at stake argues against environmental issues including temperature, altitude, and other weather conditions to explain this consistently sustained very low death toll among the curcumin consumers.
TL;DR: Bioactive compound present in Artemisia annua against, hepatitis B virus, bovine viral diarrhea virus, and Epstein–Barr virus, will be of great value if they have efficacy against SARS‐CoV‐2.
Abstract: In December 2019, a number of pneumonia cases associated with 2019 novel coronavirus occurred in Wuhan, China. Later taxonomist name the virus SARS‐CoV‐2 and disease called COVID‐19. No approved vaccine or treatment are available for this virus. Current technical guide is related to address therapeutic option for SARS‐CoV‐2. COVID‐19 is great challenge for scientist across the globe. Bioactive compound present in Artemisia annua against, hepatitis B virus, bovine viral diarrhea virus, and Epstein–Barr virus. A. annua have shown significant activity against SARS coronavirus that occur in 2002. This agent is cheap and easily available and will be of great value if they have efficacy against SARS‐CoV‐2. Scientific attention is needed toward this agent to address for the treatment of COVID‐19.
TL;DR: This review indicated that Ginkgo biloba might be efficient in the improvement of MetS; however, more studies especially clinical trials are needed to evaluate safety and efficacy of G. biloba.
Abstract: The Ginkgo biloba (G. biloba), commonly known as ginkgo, brings considerable benefit to common medicine, including weight loss effects, as well as antidiabetic, antihypertensive, and antilipidemic properties that could be effective in the treatment of Metabolic syndrome (MetS) associated with increased risk of cardiovascular disease events. Major compounds of G. biloba are terpene lactones (bilobalide and ginkgolides A, B, and C) and flavone glycosides (isorhamnetin, quercetin, and kaempferol). We evaluated the most relevant original articles to indicate the effects of G. biloba on different components of MetS, including obesity, high blood pressure, dyslipidemia, and hyperglycemia. Several electronic databases (Scopus, PubMed, Web of Science and Google Scholar) were searched and the articles that included Ginkgo's effect on one or more of the criteria for MetS were selected. This review indicated that G. biloba might be efficient in the improvement of MetS; however, more studies especially clinical trials are needed to evaluate safety and efficacy of G. biloba.
TL;DR: It is suggested that nano‐curcumin supplementation for 8 weeks was effective in reducing depression and anxiety scores in patients with diabetic polyneuropathy.
Abstract: Depression in patients with diabetes is associated with poor glycemic control and linked to an increased risk for diabetes complications such as neuropathy. Curcumin has shown potential antidepressant-like activities in some studies. The present study is the first randomized controlled trial to test the efficacy of nano-curcumin supplementation on depression, anxiety, and stress in patients with diabetic polyneuropathy. Eighty patients with diabetes were enrolled in this parallel, double-blind, randomized, placebo-controlled clinical trial. The participants were allocated randomly to the intervention (n = 40) and control (n = 40) groups. They received 80 mg of nano-curcumin or placebo capsules daily for 8 weeks. At baseline and end of study, anthropometric measurements, dietary intake, physical activity, glycemic indices, and severity of neuropathy were assessed. The depression, anxiety, and stress level were measured by Depression, Anxiety, Stress Scale (DASS-21-items) questionnaire before and after the intervention. After intervention, there was a significant reduction in the mean score of depression in the nano-curcumin group (from 16.7 [3.1] to 15.3 [2.6]) compared with placebo group (17.5 [3.2] to 17.3 [3.1]; p = .02). In addition, a significant fall was found in the mean score of anxiety in the nano-curcumin group (from 22.4 [4.03] to 20.6 [3.4]) compared with the placebo group (21.9 [3.5] to 21.2 [3.5]; p = .009). Changes in stress score were not statistically significant between the two groups. These findings suggested that nano-curcumin supplementation for 8 weeks was effective in reducing depression and anxiety scores in patients with diabetic polyneuropathy.
TL;DR: CA might be a cotreatment with DOX to ameliorate cardiotoxicity by Sirt1–NLRP3 pathway, which is reported in many bioactivities including antitumor, anti‐inflammatory, and cardioprotection.
Abstract: The limitation of doxorubicin (DOX), which is widely used for the treatment of solid tumors and hematologic malignancies, is a vital problem in clinical application. The most serious of limit factors is cardiotoxicity. Calycosin (CA), an isoflavonoid that is the major active component in Radix astragali, has been reported in many bioactivities including antitumor, anti-inflammatory, and cardioprotection. The aim of the study was to investigate the effects and mechanisms of CA on DOX-induced cardiotoxicity in vitro and in vivo. CA increased H9c2 cell viability and reduced apoptosis induced by DOX via Bcl-2, Bax, and the PI3K-Akt signaling pathway. Moreover, CA prevented DOX-induced oxidative stress in cells by decreasing the generation of reactive oxygen species. Similarly, oxidative stress was inhibited by CA through the increased activities of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase and decreased the levels of aspartate aminotransferase, lactate dehydrogenase, and malondialdehyde in vivo. Furthermore, the levels of sirtuin 1 (Sirt1)-NOD-like receptor protein 3 (NLRP3) and related proteins were ameliorated by CA in cells and in mice hearts. When H9c2 cells were treated by Ex527 (Sirt1 inhibitor), the effect of CA on expressions of NLRP3 and thioredoxin-interacting protein was suppressed. In conclusion, the results suggested that CA might be a cotreatment with DOX to ameliorate cardiotoxicity by Sirt1-NLRP3 pathway.
TL;DR: Providing novel treatments with potential anti-inflammatory, antioxidative, antiapoptotic effects, as well as ameliorative candidates on autophagy, would be grateful in preventing the progression of COVID-19.
Abstract: Dear Editor, Researchers are aware of a global pandemic on novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). It has been a serious leading cause of morbidity and mortality worldwide (Wang et al., 2020; Wu et al., 2020). Despite advancements in providing antiviral drugs, no effective treatment has now been approved for the prevention/management/ treatment of COVID-19. Therefore, there exists a dire need to discover new, safe, and more efficacious treatment options to achieve ideal results. Besides, considering the contagiousness and unabated spread of COVID-19 infection, there is considerable interest in providing novel treatments. Accordingly, natural products possess promising antiviral effects through interfering with several aspects of viral infection like viral entry, genome release processes, gene expression, and replication (Pour, Fakhri, Asgary, Farzaei, & Echeverria, 2019). Besides, several reports have indicated the crucial role of oxidative stress, inflammation, apoptosis, autophagy, in triggering the pathogenesis and complications of COVID-19. So, providing novel treatments with potential anti-inflammatory, antioxidative, antiapoptotic effects, as well as ameliorative candidates on autophagy, would be grateful in preventing the progression of COVID-19. Additionally, during the past viral infections such as SARS-CoV and influenza, natural origin based medicinal plants have been widely used for counteracting viral infections (Ang, Lee, Choi, Zhang, & Lee, 2020). Astaxanthin (3,30dihydroxy-β,β-carotene-4,40-dione) is a keto-carotenoid with a wide variety of health-promoting properties through its effects on a plethora of molecular targets (Fakhri, Yosifova Aneva, Farzaei, & SobarzoSánchez, 2019). From the mechanistic point of view, considering the antioxidant, anti-inflammatory, antiapoptosis, and autophagymodulatory activities (Fakhri, Dargahi, Abbaszadeh, & Jorjani, 2019; Heidari Khoei et al., 2019), astaxanthin underscores a great potential in alleviating the complications of COVID-19. Astaxanthin is a lipid-soluble carotenoid with a polar–nonpolar– polar structure that could easily pass through and fix into the double layers of cell membrane. While the polar zones of astaxanthin's structure scavenge free radicals inside and outside the cell membrane, its polyene chain captures radicals in the cell membrane (Augusti et al., 2012). This effect has been found to be several folds more than other antioxidants, like vitamin E (Heidari Khoei et al., 2019; Østerlie, Bjerkeng, & Liaaen-Jensen, 2000; Shimidzu, Goto, & Miki, 1996). In terms of pharmacological mechanisms, astaxanthin decreased the membrane fluidity and increased the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway (Wu et al., 2014). The pathway, in turn, elevates the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), peroxidase, thiobarbituric acid reactive substances (TBARS), NAD(P)H quinine oxidoreductase-1 (NQO-1) glutathione-S-transferase-α1 (GST-α1) (Fakhri, Abbaszadeh, Dargahi, & Jorjani, 2018). Astaxanthin also showed potential inhibitory effects on superoxide radicals, nitrogen dioxide radicals, cytosolic calcium (Otton et al., 2010), reactive oxygen species (ROS), myeloperoxidase (MPO), and other oxidative mediators, as well as lipid peroxidation (Campoio, Oliveira, & Otton, 2011; Kamath, Srikanta, Dharmesh, Sarada, & Ravishankar, 2008). All the reports, are in the way to introduce astaxanthin as a super antioxidant, which could be a promising candidate in combating COVID-19. Astaxanthin is a multi-target agent which employs several mechanisms to apply potential anti-inflammatory effects. For instance, astaxanthin reduced the expression of N-methyl-D-aspartate receptor subtype 2B (NR2B), tumor necrosis factor-α (TNF-α), p-p38 mitogenactivated protein kinase (MAPK) (Fakhri, Dargahi, Abbaszadeh, & Jorjani, 2018), p-extracellular signal-regulated kinases (p-ERK)/ERK, and increased p-Akt/Akt to modulate inflammation (Fakhri, Dargahi, et al., 2019). Astaxanthin also suppressed nuclear factor-κB (NF-κB) and down-stream mediators, including interleukin (IL)-6, IL-1β, matrix metalloproteinase (MMP-9) (Bhuvaneswari, Yogalakshmi, Sreeja, & Anuradha, 2014; Speranza et al., 2012), nitric oxide (NO), and cyclooxygenase-2 (COX-2) (Choi, Park, Choi, & Chang, 2008). The modulatory effects of astaxanthin on the phosphoinositide 3-kinases (PI3K)/Akt, ERK/MAPK, and the up-stream macrophage migration inhibitory factor (MIF) has also been shown regarding its antiinflammatory effects (Fakhri, Abbaszadeh, et al., 2018). Considering the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) in the initiation of interferonstimulated response elements (ISRE), attenuating the pathway would play a pivotal role in preventing the inflammation occurs in COVID19. In this regard, the inhibitory effects of astaxanthin on JAK2/ STAT3 has been revealed (Kowshik et al., 2014). All the pharmacological and mechanistic evidence are confirming a bright future for astaxanthin to be used against the destructive inflammatory pathways then related complications in COVID-19. Growing evidence is also making a precise association between the therapeutic effects of astaxanthin and its antiapoptotic properties (Fakhri, Yosifova Aneva, et al., 2019). Astaxanthin exerted antiapoptotic effects by inhibiting Bax/Bcl-2, and caspases-3/9 (Masoudi et al., 2017). Astaxanthin also reduced apoptosis through PI3K/Akt pathway to Received: 13 June 2020 Revised: 21 June 2020 Accepted: 22 June 2020