The methanol, n-butanol, chloroform and water extracts obtained from the root of Eurycoma longifolia Jack were assayed using methylene blue assay to evaluate its cytotoxic effect against KB, DU-145, RD, MCF-7, CaOV-3, MDBK cell lines. The results showed that all the root extracts except the water extract of E. longifolia produced significant cytotoxic effect on these cell lines. However, no significant cytotoxic effect was detected on MDBK (kidney) normal cell line. 9-methoxycanthin-6-one, an alkaloid, was detected in each extract with different intensities by reversed-phase high performance liquid chromatography.
The butanol, methanol, water and chloroform extracts of the roots of Eurycoma longifolia Jack were studied using various tests of potency of treated male rats. The results showed that E. longifolia produced a dose-dependent, recurrent and significant increase in the episodes of penile reflexes as evidenced by increases in quick flips, long flips and erections of the treated male rats during the 30 min observation period. These results provide further evidence that E. longifolia increases the aphrodisiac potency activity in treated animals.
Obesity is one of the most serious public health problems in both developed and developing countries in recent years. While lifestyle and diet modifications are the most important management strategies of obesity, these may be insufficient to ensure long-term weight reduction in certain individuals and alternative strategies including pharmacotherapy need to be considered. However, drugs option remains limited due to low efficacy and adverse effects associated with their use. Hence, identification of safe and effective alternative therapeutic agents remains warranted to combat obesity. In recent years, bioactive phytochemicals are considered as valuable sources for the discovery of new pharmacological agents for the treatment of obesity. Adipocyte hypertrophy and hyperplasia increases with obesity and undergo molecular and cellular alterations that can affect systemic metabolism giving rise to metabolic syndrome and comorbidities such as type 2 diabetes and cardiovascular diseases. Many phytochemicals have been reported to target adipocytes by inhibiting adipogenesis, inducing lipolysis, suppressing the differentiation of preadipocytes to mature adipocytes, reducing energy intake, and boosting energy expenditure mainly in vitro and in animal studies. Nevertheless, further high-quality studies are needed to firmly establish the clinical efficacy of these phytochemicals. This review outlines common pathways involved in adipogenesis and phytochemicals targeting effector molecules of these pathways, the challenges faced and the way forward for the development of phytochemicals as antiobesity agents.
Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)-Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P-glycoprotein (P-gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid-based solid dispersion (TAF2-SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2-SD-treated rats showed significantly twofold (p
The effect of scopoletin-standardized Morinda elliptica leaf extract against osteoarthritis was investigated in ex vivo explant culture and preclinical rodent model. Thirty male rats were grouped (n = 6) into untreated osteoarthritis (OA), OA + Diclofenac (5 mg/kg), and OA + extract (200 and 400 mg/kg) and compared with healthy control. Monosodium iodoacetate were injected into the right intra-articular knee joints to induce OA. The rats were evaluated for OA severity via physical (micro-CT and histological observations), biochemical, ELISA, and mRNA expression analysis (for inflammation and cartilage degradation biomarkers), after 28 days of treatment. The extract suppressed glycosaminoglycan release from the cartilage explant in the presence of Interleukin-1β. The 200 mg/kg dose appeared better than 400 mg/kg dose, at reducing cartilage and subchondral bone erosions in OA-induced rats, by significantly down-regulating the collagenases and aggrecanase. The extract dose-dependently reduced serum inflammation biomarkers and increased bone formation biomarkers to near normal levels in the OA-induced rats. M. elliptica leaf scopoletin-standardised extract alleviated OA progression and articular cartilage structure, by ameliorating cartilage degradation, nitric oxide levels, inflammation, bone /cartilage homeostasis, collagenase/aggrecanase activities, chondrocytes survival, subchondral bone structure and integrity.
A systematic review and network-meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus other comparators (i.e., placebo/control/other galactagogues). A pairwise comparison for the treatment effect was carried out to generate the forest plot for the NMA. League tables were generated using treatment effect, weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise comparisons, where WMD > 0 favors the column-defining treatment. Five studies were identified with 122 participants receiving treatment with fenugreek. The NMA results of 4 studies indicated that consumption of fenugreek significantly increased amount of the produced breast milk [11.11, CI 95% 6.77, 15.46] versus placebo. The pairwise comparison revealed that fenugreek was effective as a galactagogue compared to placebo, control, and reference groups WMD 17.79 [CI 11.71, 23.88]. However, the effect of fenugreek was substantially inferior to Coleus amboinicus Lour and palm date. The NMA using pairwise comparison demonstrated the effect of C. amboinicus and palm date in the stimulation of the breast milk production was comparable and superior to all comparators.
The traditional practice of eating the flowers of Clitoria ternatea L. or drinking their infusion as herbal tea in some of the Asian countries is believed to promote a younger skin complexion and defend against skin aging. This study was conducted to investigate the protective effect of C. ternatea flower water extract (CTW) against hydrogen peroxide-induced cytotoxicity and ultraviolet (UV)-induced mitochondrial DNA (mtDNA) damage in human keratinocytes. The protective effect against hydrogen peroxide-induced cytotoxicity was determined by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and mtDNA damage induced by UV was determined by polymerase chain reaction. Preincubation of HaCaT with 100, 250, and 500 μg/ml CTW reduced cytotoxicity effects of H2 O2 compared with control (H2 O2 alone). CTW also significantly reduced mtDNA damage in UV-exposed HaCaT (p
In this study, a series of 20 structurally similar vanilloids (Vn) were tested for their antiproliferative effects against 12 human cancer cells: human breast (MCF-7 and MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29 and HCT116), nasopharyngeal (CNE-1 and HK-1), and leukemic (K562 and CEM-SS) cancer cells. Among all the tested vanilloids, Vn16 (6-shogaol) exhibited the most potent cytotoxic effects against human colorectal cancer cells (HT-29). The apoptotic induction effects exhibited by Vn16 on HT-29 cells were confirmed using dual staining fluorescence microscopy and enzyme-linked immunosorbent assay. The effects of Vn16 on regulation of 43 apoptotic-related markers were determined in HT-29. The results suggested that 8 apoptotic markers (caspase 8, BAD, BAX, second mitochondrial-derived activator, caspase 3, survivin, bcl-2, and cIAP-2) were either upregulated or downregulated. These results further support the chemopreventive properties of foods that contain vanilloids.
Bioactive compounds of Eurycoma longifolia (EL) jack were previously shown to reduce omentum fat mass and oestradiol-induced fatty uterine adhesion in rats. However, the exact role of EL on adipogenesis remains unknown. This study sought to investigate the effects of an EL standardized quassinoids-enriched fraction (SQEL) and the pure compound, eurycomanone, on adipogenesis in 3T3-L1 preadipocyte cells. 3T3-L1 cells were induced to differentiate and treated for 8 days. The treatment reduced intracellular accumulation of lipid droplets and triglycerides in the differentiating adipocytes and induced lipolysis in matured adipocytes. The expressions of adipogenic transcription factors and markers were also significantly downregulated during the early stage of differentiation. Furthermore, SQEL also suppressed body weight gain, decreased epididymal and perirenal fat pad mass and size, and reduced the accumulation of fat in the livers of C57BL/6J mice fed with normal or high-fat diet that were concurrently given 5 mg/kg and 10 mg/kg (i.p) of SQEL for 12 weeks. SQEL also improved glucose intolerance and decreased the elevated total cholesterol and triglyceride levels in these mice groups. These findings suggest that SQEL could be explored as an alternative pharmacologic agent inhibiting adipogenesis for the prevention of obesity.
Piper longum (family Piperaceae), commonly known as "long-pepper" or "Pippali" grows as a perennial shrub or as an herbaceous vine. It is native to the Indo-Malaya region and widely distributed in the tropical and subtropical world including the Indian subcontinent, Sri Lanka, Middle-East, and America. The fruits are mostly used as culinary spice and preservatives and are also a potent remedy in various traditional medicinal systems against bronchitis, cough, cold, snakebite, and scorpion-sting and are also used as a contraceptive. Various bioactive-phytochemicals including alkaloids, flavonoids, esters, and steroids were identified from the plant extracts and essential oils from the roots and fruits were reported as antimicrobial, antiparasitic, anthelminthic, mosquito-larvicidal, antiinflammatory, analgesic, antioxidant, anticancer, neuro-pharmacological, antihyperglycaemic, hepato-protective, antihyperlipidaemic, antiangiogenic, immunomodulatory, antiarthritic, antiulcer, antiasthmatic, cardioprotective, and anti-snake-venom agents. Many of its pharmacological properties were attributed to its antioxidative and antiinflammatory effects and its ability to modulate a number of signalling pathways and enzymes. This review comprehensively encompasses information on habit, distribution, ethnobotany, phytochemistry, and pharmacology of P. longum in relation to its medicinal importance and health benefits to validate the traditional claims supported by specific scientific experiments. In addition, it also discusses the safety and toxicity studies, application of green synthesis and nanotechnology as well as clinical trials performed with the plant also elucidating research gaps and future perspectives of its multifaceted uses.
The worldwide spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to health, economic, environmental, and social aspects of human lives. Currently, there are no approved treatments that can effectively block the virus although several existing antimalarial and antiviral agents have been repurposed and allowed use during the pandemic under the emergency use authorization (EUA) status. This review gives an updated overview of the antiviral effects of phytochemicals including alkaloids, flavonoids, and terpenoids against the COVID-19 virus and their mechanisms of action. Search for natural lead molecules against SARS-CoV-2 has been focusing on virtual screening and in vitro studies on phytochemicals that have shown great promise against other coronaviruses such as SARS-CoV. Until now, there is limited data on in vivo investigations to examine the antiviral activity of plants in SARS-CoV-2-infected animal models and the studies were performed using crude extracts. Further experimental and preclinical investigations on the in vivo effects of phytochemicals have to be performed to provide sufficient efficacy and safety data before clinical studies can be performed to develop them into COVID-19 drugs. Phytochemicals are potential sources of new chemical leads for the development of safe and potent anti-SARS-CoV-2 agents.
Emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, COVID-19, has become the global panic since December 2019, which urges the global healthcare professionals to identify novel therapeutics to counteract this pandemic. So far, there is no approved treatment available to control this public health issue; however, a few antiviral agents and repurposed drugs support the patients under medical supervision by compromising their adverse effects, especially in emergency conditions. Only a few vaccines have been approved to date. In this context, several plant natural products-based research studies are evidenced to play a crucial role in immunomodulation that can prevent the chances of infection as well as combat the cytokine release storm (CRS) generated during COVID-19 infection. In this present review, we have focused on flavonoids, especially epicatechin, epigallocatechin gallate, hesperidin, naringenin, quercetin, rutin, luteolin, baicalin, diosmin, ge nistein, biochanin A, and silymarin, which can counteract the virus-mediated elevated levels of inflammatory cytokines leading to multiple organ failure. In addition, a comprehensive discussion on available in silico, in vitro, and in vivo findings with critical analysis has also been evaluated, which might pave the way for further development of phytotherapeutics to identify the potential lead candidatetoward effective and safe management of the SARS-CoV-2 disease.
A sudden outbreak of the COVID-19 pandemic was a big blow to the world community on every level. Created by a novel coronavirus, SARS-CoV-2, which was previously unknown to the human immune system. The expert opinion almost immediately united on the fact that the most effective way of fighting the pandemic would be by building immunity artificially via a mass immunization program. However, it took about a year for the approval of the first vaccine against COVID-19. In the meantime, a big part of the general population started adapting nutritious diet plans and dietary supplements to boost natural immunity as a potential prophylactic strategy against SARS-CoV-2 infection. Whether they originate from mainstream medicine, such as synthetic supplements, or traditional herbal remedies in the form of single or poly-herbs, these supplements may comprise various components that exhibit immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial characteristics. There is a substantial body of predictions and expert opinions suggesting that enhancing one's diet with dietary supplements containing additional nutrients and bioactive compounds like vitamins, minerals, amino acids, fatty acids, phytochemicals, and probiotics can enhance the immune system's ability to develop resistance against COVID-19, although none of them have any conclusive evidence nor officially recommended by World Health Organization (WHO). The current review critically acclaims the gap between public perception-based preference and real evidence-based study to weigh the actual benefit of dietary supplements in relation to COVID-19 prevention and management.
Oxidative stress is implicated in the initiation, pathogenesis, and progression of various gastric inflammatory diseases (GID). The prevalence of these diseases remains a concern along with the increasing risks of adverse effects in current clinical interventions. Hence, new gastroprotective agents capable of inhibiting oxidative stress by modulating cellular defense systems such as the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway are critically needed to address these issues. A candidate to solve the present issue is xanthone, a natural compound that reportedly exerts gastroprotective effects via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Moreover, xanthone derivatives were shown to modulate the Nrf2/ARE signaling pathway to counter oxidative stress in both in vitro and in vivo models. Thirteen natural xanthones have demonstrated the ability to modulate the Nrf2/ARE signaling pathway and have high potential as lead compounds for GID as indicated by their in vivo gastroprotective action-particularly mangiferin (2), α-mangostin (3), and γ-mangostin (4). Further studies on these compounds are recommended to validate the Nrf2 modulatory ability in relation to their gastroprotective action.
The anti-inflammatory and immunosuppressive activities of plant secondary metabolites are due to their diverse mechanisms of action against multifarious molecular targets such as modulation of the complex immune system associated with rheumatoid arthritis (RA). This review discussed and critically analyzed the potent anti-inflammatory and immunosuppressive effects of several phytochemicals and their underlying mechanisms in association with RA in experimental studies, including preliminary clinical studies of some of them. A wide range of phytochemicals including phenols, flavonoids, chalcones, xanthones, terpenoids, alkaloids, and glycosides have shown significant immunosuppressive and anti-inflammatory activities in experimental RA models and a few have undergone clinical trials for their efficacy and safety in reducing RA symptoms and improve patient outcomes. These phytochemicals have potential as safer alternatives to the existing drugs in the management of RA, which possess a wide range of serious side effects. Sufficient preclinical studies on safety and efficacy of these phytochemicals must be performed prior to proper clinical studies. Further studies are needed to address the barriers that have so far limited their human use before the therapeutic potential of these plant-based chemicals as anti-arthritic agents in the treatment of RA is fully realized.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti-inflammatory and antioxidant properties. This review aims to synthesize current preclinical data on the anti-neuroinflammatory mechanisms of curcumin in the context of AD, addressing its pharmacokinetics, bioavailability, and potential as a therapeutic adjunct. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in AD. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro-inflammatory cytokines. Despite its potential, challenges remain regarding its limited bioavailability and the scarcity of comprehensive human clinical trials. Curcumin emerges as a promising therapeutic adjunct in AD due to its multimodal neuroprotective benefits. However, further research is required to overcome challenges related to bioavailability and to establish effective dosing regimens in human subjects. Developing novel delivery systems and formulations may enhance curcumin's therapeutic potential in AD treatment.
Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L-NG-nitro arginine methyl ester (L-NAME), an analog of L-arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L-NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L-NAME-induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L-NAME-induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin-converting enzyme (ACE) and endothelin-1. Moreover, they exhibit anti-inflammatory effects, attenuating inflammation-mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L-NAME-induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.
It is suggested that supplementation with silymarin (SIL) has beneficial impacts on kidney and liver functions. This systematic review and dose-response meta-analysis assessed the impact of SIL administration on certain hepatic, renal, and oxidative stress markers. A systematic search was conducted in various databases to identify relevant trials published until January 2023. Randomized controlled trials (RCTs) that evaluated the effects of SIL on kidney and liver markers were included. A random-effects model was used for the analysis and 41 RCTs were included. The pooled results indicated that SIL supplementation led to a significant reduction in serum levels of alkaline phosphatase, alanine transaminase, creatinine, and aspartate aminotransferase, along with a substantial elevation in serum glutathione in the SIL-treated group compared to their untreated counterparts. In addition, there was a nonsignificant decrease in serum levels of gamma-glutamyl transferase, malondialdehyde (MDA), total bilirubin, albumin (Alb), total antioxidant capacity, and blood urea nitrogen. Sub-group analyses revealed a considerable decline in MDA and Alb serum values among SIL-treated participants with liver disease in trials with a longer duration (≥12 weeks). These findings suggest that SIL may ameliorate certain liver markers with potential hepatoprotective effects, specifically with long-term and high-dose supplementation. However, its nephroprotective effects and impact on oxidative stress markers were not observed. Additional high-quality RCTs with longer durations are required to determine the clinical efficacy of SIL supplementation on renal and oxidative stress markers.
Recently, dermatology has increasingly focused on understanding skin aging and exploring novel therapeutic approaches. Despite progress in cosmetic and pharmaceutical research, a significant gap remains in comprehensively understanding the effects and mechanisms of herbal extracts on skin aging. While many studies have examined the bioactivities of herbal compounds in preclinical models, comprehensive human trials have been scarce over the past decade. This review aims to address this gap by synthesizing human trials from the past decade, focusing on the therapeutic effects of herbal extracts on skin aging. The objective is to unravel the mechanisms contributing to skin aging and assess the therapeutic potential of herbal compounds. Following the PRISMA 2020 guideline, a systematic review was performed across OvidMEDLINE, Cochrane Central Register of Controlled Trials, and Embase via Ovid. A meticulous search strategy identified relevant clinical trials. The review highlights the essential role of herbal compounds in skin aging, particularly their antioxidant activity in suppressing the aging process. Analysis of 51 clinical trials offers valuable insights into their diverse effects on skin aging parameters. Herbal compounds are promising alternatives to synthetic products for treating skin aging. Their demonstrated efficacy in mitigating wrinkles, enhancing elasticity, maintaining hydration, and controlling pigmentation underscores their potential in developing antiaging therapeutics. However, further studies are needed to identify specific compounds responsible for these effects and understand their mechanisms. Future directions include conducting large-scale trials, exploring synergies with other ingredients, and optimizing delivery systems for sustainable, effective antiaging therapies.