Inhibitory effects of phytochemicals on NLRP3 inflammasome activation: A review

BackgroundThe NLRP3 inflammasome formation and following cytokine secretion is a crucial step in innate immune responses. Internal and external factors may trigger inflammasome activation and result in inflammatory cytokine secretion. Inflammasome formation and activity play critical roles in several disease pathologies such as cardiovascular, metabolic, renal, digestive, and CNS diseases. Underlying pathways are not yet clear, but phytochemicals as alternative therapies have been extensively used for suppression of inflammatory responses.PurposeIn this review, we aimed to summarize in vivo and in vitro effects on NLRP3 inflammasome activation of selected phytochemicals.MethodThree phytochemicals; Sulforaphane, Curcumin, and Resveratrol were selected, and studies were reviewed to clarify their intracellular signaling mechanism in NLRP3 inflammasome activity. PubMed and Scopus databases are used for the search. For sulforaphane, 8 articles, for curcumin, 25 articles, and for resveratrol, 41 articles were included in the review.ConclusionIn vitro and in vivo studies pointed out that the selected phytochemicals have inhibitory properties on NLRP3 inflammasome activity. However, neither the mechanism is clear, nor the study designs and doses are standardized.     

Isolation and characterization of microsatellite markers in Indian neem (Azadirachta indica var. indica A. Juss) and cross-amplification in Thai neem (A. indica var. siamensis Valenton)

We developed eight polymorphic microsatellite loci in Indian neem (Azadirachta indica var. indica) and cross-amplified in closely related species Thai neem (A. indica var. siamensis). The number of alleles per locus in Indian neem and Thai neem ranged from 3 to 9 and 3 to 9, respectively. Average observed and expected heterozygosities in Indian neem and Thai neem were 0.63 and 0.70 and 0.61 and 0.65, respectively. Two loci exhibited significantly fewer heterozygotes than expected under Hardy–Weinberg equilibrium. These microsatellites may provide a useful tool for population genetics to establish conservation and management strategy.     

Potential of the neem tree (Azadirachta indica) for pest control and rural development

The neem tree (Azadirachta indica) contains promising pest-control substances found effective against many economically important pests. These materials are easy to process by village-level industries and easy to use by limited-resource farmers, thereby offering potential for crop protection and off-farm income generation. The tree’s numerous pharmacological and other complementary uses make it doubly attractive for incorporation in large-scale rural development efforts.     

Challenges to using neem (Azadirachta indica var. sianensis Valenton) in Thailand

The use of botanical insecticides based on the neem seed (Azadirachta indica var.siamensis Valeton) shows strong potential in the fight against important agricultural pests. Unfortunately, its use in rural Thailand is extremely limited. This study examines the efficacy of neem extracts processed under rural conditions; identifies factors that influence local farmers’ adoption of neem products; and proposes recommendations to promote the use of neem insecticides. The principal findings are: in field trials conducted under typical rural conditions, neem did not adequately control major pests of yard-long beans (Vigna sesquipedalis); and intensity of vegetable production, knowledge of neem insecticides and availability and accessibility of neem products strongly influence farmers’ adoption of neem products for pest control.     

In-vitro phytochemical and pharmacological bio-efficacy studies on Azadirachta indica A. Juss and Melia azedarach Linn for anticancer activity

In this study, phyto-constituents, anti-bacterial and anticancer activity of Azadirachta indica A. Juss and Melia azedarach Linn was analyzed. High Performance Liquid Chromatography (HPLC) and Thin Layer Chromatography (TLC) fingerprint profile of methanol extract of A. indica and M. azedarach was carried out. The present findings showed the presence of phytochemicals such as, steroids, alkaloids, phenols, flavonoids, saponins, tannins, anthraquinone and aminoacids in A. indica and M. azedarach extracts. HPLC profiling of methanolic extract of A. indica and M. azaderach revealed eleven and ten fractions of compounds were visualized in the form of peak. In TLC methanolic extract of A. indica was separated by eight distinct phenolic and three steroidal bands and M. azaderach showed sixteen distinct phenolic and three different steroidal bands. In antibacterial activity, Among the various extracts 50 µg/ml methanolic extracts of A. indica showed high activity against K. pneumoniae (14 mm) and M. azedarach showed high activity against S. aureus (15 mm). The results suggest that the crude methanolic extracts of A. indica and M. azedarach possess significant phytochemical properties compared to other extracts and hence the phytochemicals of M. azedarach and A. indica can be exploited for plant based anticancer and antimicrobial agents in the near future.     

Identification of 24-methylenelophenol from heartwood of Azadirachta indica

24-Methylenelophenol was identified from the heartwood of the neem tree, Azadirachta indica.     

Nimbidiol,a modified diterpenoid of the root-bark of Azadirachta indica

Nimbidiol, a modified diterpenoid, isolated from the root-bark of Azadirachta indica (Indian ‘neem’), was characterized by spectroscopic method     

Terminalia bellirica (Gaertn.) roxb. (Bahera) in health and disease: A systematic and comprehensive review

BackgroundTerminalia bellirica (Gaertn.) Roxb. is one of the oldest medicinal herbs of India, Pakistan, Nepal, Bangladesh and Sri Lanka as well as South-East Asia. Its medicinal utility has been described in the different traditional medicinal systems, such as Ayurveda, Unani, Siddha, and traditional Chinese medicine.PurposeThe present study is aimed at providing a comprehensive overview on the traditional medicinal use, major phytoconstituents, biological and pharmacological activities and related mechanisms of actions and clinical studies of T. bellirica. Another objective is to describe current limitations and future direction of T. bellirica-related research.MethodsPubMed, ScienceDirect, Scopus, Cochrane Library, and EBOSCO host databases were selected to explore literature published between 1980 and 2020 (till March). Keywords used in various combinations comprised of Terminalia bellirica, phytoconstituents, health effects, pharmacological activities, molecular targets, in vitro, in vivo, clinical studies, and disease prevention.ResultsA broad spectrum in vitro and in vivo studies suggested various biological and pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, hepatoprotective, renoprotective, antidiabetic, anti-hyperlipidemic, and anticancer activities. Diverse bioactivities of T. bellirica have been ascribed to the presence of many bioactive phytochemicals, such as glucoside, tannins, gallic acid, corilagin, ellagic acid, ethyl gallate, galloyl glucose, chebulagic acid, and arjunolic acid.ConclusionPreclinical and clinical studies have suggested that T. bellirica plant and its phytoconstituents have immense potential for prevention and treatment of various diseases. Additional in vivo studies and clinical trials are warranted to realize the complete medicinal attributes of this plant.     

Anti-inflammatory natural products as potential therapeutic agents of rheumatoid arthritis: A systematic review

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease causing severe locomotor disability and deterioration in the quality of life. Existing treatments for RA mainly focus on the use of immunomodulators and the suppression of synovial inflammation, and many have significant side effects. Medicinal plants are regarded as important alternative sources for treating RA.PurposeThis review summarizes the bioactive compounds of medicinal plants, which have been shown to modulate the immune response by regulating interleukins in vitro and in vivo experimental models, and that may be promising substances for use in the treatment of RA.MethodsArticles on natural products used for the management of arthritis were retrieved from PubMed, Embase, Scopus, and Web of Science through electronic and manual search in English. In total, 576 publications were identified, and 34 were included in this systematic review.ResultsTwo articles presented findings on the role of natural components in the treatment of arthritis in both in vitro and in vivo studies. Nine reports defined the role of plant-derived natural molecules in the treatment of arthritis using cell lines, and 27 in vivo studies assessed the anti-arthritic efficacy and immunomodulation effects of phytoconstituents on interleukin production and inflammatory responses.ConclusionThis systematic review broadly reports that, in contrast to other classes of phytochemicals, flavonoids have the greatest therapeutic potential against arthritis by modulating the expression of pro-inflammatory TNF-α, IL-1β, IL-6, IL-8, and IL-17, as well as anti-inflammatory IL-2 and IL-10 cytokines, through the suppression of dynamic inflammatory biomarkers.     

Azadirachta indica (neem) leaf dietary effects on the immunity response and disease resistance of Asian seabass,Lates calcarifer challenged with Vibrio harveyi

The present study was aimed to address the possible evaluation of Azadirachta indica (neem) leaf-supplemented diets on innate immune response in Asian seabass, Lates calcarifer fingerlings against Vibrio harveyi infection. Fish were fed for two weeks diets containing six graded levels of neem leaf at 0 g, 1 g, 2 g, 3 g, 4 g and 5 g per kg feed. Fish fed neem leaf-supplemented diet displayed significant differences (p < 0.05) in weight gain, specific growth rate (SGR) and feed conversion ratio (FCR) compared to the control group fed without neem leaf-supplemented diet. Various innate immune parameters were examined pre-challenge and post-challenge. Fish was injected intraperitoneally with a lethal dose of V. harveyi containing 10⁸ cells mL^?1. Supplementation of neem leaf diet significantly increased phagocytic activity, superoxide anion production, serum lysozyme, serum bactericidal activity, serum anti-protease activity throughout the experimental period when compared with the control group. Dietary doses of neem leaf diet significantly influenced the immune parameters, haematological parameters and blood biochemical indices of treated fish. The results suggested that fish fed neem leaf-supplemented diet improved the immune system and increased survival rate in L. calcarifer fingerlings against V. harveyi infection.     

Tribulus terrestris and female reproductive system health: A comprehensive review

BackgroundTribulus terrestris L. (T. terrestris) positive performance on the male sexual system has been confirmed, but little is known about its effects on the female reproductive system.PurposeThis review discussed in detail the beneficial impact of T. terrestris and its secondary metabolites on the female reproductive system.Study design and methodsIn this review, the scientific Databases of Science direct, Pubmed, Web of Science, Google, Google Scholar, Researchgate, EMBASE, Scientific Information (SID), and Elsevier were searched profoundly. Studies about the pharmacological activities of T. terrestris on the female reproductive system in each aspect of investigations: human, in vivo, and in vitro studies, in the period from 1998 to 2020 were admitted. Our study was not limited by the language of publications.Results23 articles about the effects of T. terrestris on the female reproductive system were found. These studies approved the T. terrestris efficacy on improvements in histological features of the ovary and uterus of polycystic ovary syndrome patients as well as the well-working of normal ovaries, enhancements in the sexual desire of postmenopausal syndrome, improve ovarian and breast cancers.ConclusionThese studies showed that the positive effect of T. terrestris on the female reproductive system was due to the presence of a secondary metabolite called protodioscin; a steroidal saponin compound, as the dominant active component of this plant.     

Echinacea in hepatopathy: A review of its phytochemistry,pharmacology, and safety

BackgroundEchinacea, one of the most popular herbs with double function of immunity and anti-inflammatory activity, has now attracted much interest for a possible alternative for the treatment of hepatopathy. This review is aimed at providing a comprehensive overview of Echinacea regarding its chemical composition, pharmacological action against various hepatopathy, and safety.MethodsA comprehensive search of published articles was conducted to focus on original publications related to Echinacea and hepatopathy till the end of 2020 using various literature databases, including China National Knowledge Infrastructure, PubMed, and Web of Science database.ResultsEchinacea exhibited excellent activities in resisting a variety of hepatopathy induced by different causes in preclinical experiments and clinical trials by regulating cell proliferation and apoptosis, antioxidant defense mechanism, voltage-gated sodium channels, lipid metabolism, circadian rhythm, p38 MAPK signaling pathway, JNK signaling pathway, Nrf2/HO-1 signaling pathway, PI3K/AKT signaling pathway, and Akt/GSK3 beta signaling pathways. The high efficacy of Echinacea is related to its immunomodulatory and anti-inflammatory activities. The main ingredients of Echinacea include caffeic acid derivatives, alkylamides, and polysaccharides, which have been well established in preclinical studies of liver diseases. Studies on acute and subacute toxicity show that Echinacea preparations are well-tolerated herbal medicines.ConclusionEchinacea may offer a novel potential strategy for clinical prevention and treatment of liver diseases and related diseases. Extensive studies are necessary to identify the underlying mechanisms and establish future therapeutic potentials of this herb. Well-designed clinical trials are still warranted to confirm the safety and effectiveness of Echinacea for hepatopathy.     

In vitro screening of systemic fungicides against Phomopsis azadirachtae,the incitant of die-back of neem

Abstract

Phomopsis azadirachtae Sateesh, Bhat & Devaki is the causal organism of die-back of neem (Azadirachta indica A.Juss.) which is, presently, a major crippling disease of neem in India. Six systemic fungicides such as Bavistin (carbendazim), Contaf (hexaconazole), Beam (tricyclazole), Fuji-one (isoprothiolane) Roko (thiophanate methyl) and Downymil (metalaxyl) were evaluated against P. azadirachtae under in vitro conditions. Colony diameter, mycelial dry weight, pycnidial formation and the germ tube length of the pathogen were the parameters studied. The results indicated that carbendazim was the most effective in inhibiting the growth followed by thiophanate methyl. Among the different concentrations tested, carbendazim at 0.25 ppm and thiophanate methyl at 0.75 ppm were optimum for controlling the growth of the pathogen. Both these fungicides can be utilized for the control of die-back of neem.     

Tetranortriterpenoids from the seeds of Azadirachta indica

Six new tetranortriterpenoids have been isolated from the extract of neem seeds. The C-7 benzoates of tetranortriterpenoids occurring in Azadirachta indica are described for the first time. The structures of all new compounds were determined by spectroscopical methods.     

Canadian contributions to research on neglected tropical diseases

BackgroundThe World Health Organization’s (WHO) Neglected Tropical Disease (NTD) Road Map for 2021–2030 was recently endorsed by all member states at the World Health Assembly in November 2020. Although only 3 of the 20 NTDs are endemic in Canada (i.e., echinococcosis, rabies, and scabies), the Canadian research community has contributed to advancing the knowledge base of all 20 NTDs. Previous research comprehensively detailed Canadian research on 11 NTDs between 1950 and 2010 using a network analysis approach. The specific objective of the present analysis was to update the publication record over the last decade (2010–2019) to include all 20 NTDs.Materials and methodsA bibliometric analysis was conducted in Scopus and Web of Science databases (for English or French articles published between January 1, 2010 and December 31, 2019) using appropriate search terms for each of the 20 NTDs and where at least 1 of the authors had a Canadian institution address. A 21st search was added to include publications including multiple NTDs or a discussion of NTDs in general. Following assessment of inclusion and exclusion criteria, 2 reviewers independently screened all abstracts, with discordant observations rereviewed to arrive at an agreement. Duplicates were removed.ResultsA total of 1,790 publications were retrieved (1,738 with a disease–specific NTD focus and 52 with a general NTD focus, resulting in 1,659 unique publications), giving an average of over 160 articles per year. Over 80% were classified as full–length research articles. The top 3 journals in terms of frequency were PLOS Neglected Tropical Diseases, PLOS ONE, and the American Journal of Tropical Medicine and Hygiene. Authors’ institutions were from all Canadian provinces. While all 20 NTDs were addressed in these publications, the 5 most commonly studied were leishmaniasis, dengue fever and chikungunya, Chagas disease, soil–transmitted helminthiases, and rabies.ConclusionsCanadian researchers across the country have contributed to the evidence base of all 20 NTDs, publishing an average of over 160 publications per year between 2010 and 2019. As WHO NTD Road Map 2021–2030 rolls out globally, the Canadian research community, in collaboration with its partners and in solidarity with people living in vulnerable circumstances in endemic regions worldwide, is well positioned to meet future research challenges so that the goal of eliminating the disease burden attributable to NTDs can be achieved.     

Evaluation of antifertility potential of Piper betle (Petiole) on female wistar rats “rising approaches of herbal contraception’’

Piper betle (Petiole) is used of herbal methods for fertility regulation is widely accepted alternative for the synthetic drugs containing chemical having side effects. Piper betle (Petiole) is the plant having several medical properties but no reports were available on the antifertility activity. The aim of this study was to investigate the antifertility activity of extracts of Piper betle (Petiole) on female wistar rats at the doses 500 mg/kg b.wt./day for 30 days. Different parameters were studied in female wistar rats including effect of Reproductive outcome, Anti-implantation, Abortifacient and Estrogenic & Anti-estrogenic activity, were observed. Piper betle shown positive test for Alkaloids, Steroid, Flavonoids, Terpene, Carbohydrates and Tannin. The extract has anti-fertility effect the control rats showed good number of litters and treatment of animal with different extracts resulted a significant (P < 0.05, P < 0.01). Antifertility activity 51% and 37.2% was exhibited by Alcoholic extracts of Piper betle (Petiole) APB and Aqueous extracts of Piper betle (Petiole) WPB respectively. After 21 days of the extracts free period, the antifertility effect of the extracts was reversed. The extract treatment with APB, an increase in the percentage of resorption index indicates the failure in development of embryo. The mean percentage of anti-implantation and abortifacient were found to be highest for APB-38.45%, WPB 13.62, and APB-28.96%, WPB-12.75% respectively. The decrement in implantation caused by the extracts may be due to estrogenic or anti-estrogenic activity. However, along with standard APB exhibiting more potent estrogenic and less potent anti-estrogenic when compared with standard. Female antifertility agents should include acceptability, safety and efficacy during and after the treatment. The above results revealed the potential, reversible female antifertility effect of alcoholic extract Piper betle (Petiole).     

Mouse sperm-egg interaction in vitro in the presence of neem oil

In vitro evidence is presented showing toxicity of neem oil on sperm-egg interaction in mouse. Cumulus oophorus-enclosed ova, inseminated with capacitated spermatozoa, were cultured in 1 ml of in vitro fertilization (IVF) medium and overlayered by 1 ml of different concentrations of neem oil (1, 5, 10, 25, 50 and 100%) for IVF duration of 4h. At the end of incubation, ova were allowed to grow in neem oil-free culture medium and assessed for fertilization, first cleavage (2-cell formation) and blastocyst formation in vitro at 4–14h, 24h and 108h post-insemination respectively. The study showed that the presence of neem oil at concentrations of 10, 25 and 50% caused inhibition of IVF in a dose-dependent manner. The toxic effect of exposure of 25 and 50% neem oil was further carried over to the first cleavage of the resulting fertilized ova and the toxic effect of 5, 10, 25, and 50% was carried over to the blastocyst formation from the resulting fertilized ova when grown in neem-oil free culture medium. A total of 94.1% inhibition of 2-cell formation and 100% inhibition of blastocyst formation from the inseminated ova was observed in 50 and 25% neem oil-treated groups respectively. Neem oil at 100% concentration caused 100% degeneration of ova at 1h of sperm-ova coculture. The study showed a direct toxic effect of neem oil on sperm-egg interaction in vitro and encourages research investigations of this herbal product as a pre-coital contraceptive.     

Leaf extract of neem (Azadirachta indica) alleviates adverse effects of drought in quinoa (Chenopodium quinoa Willd.) plants through alterations in biochemical attributes and antioxidants

The influence of varying concentrations (0, 1, 3, 4, 5, 6, 8, and 10 % v/v) of neem (Azadirachta indica) leaf extract on drought stressed (40 % field capacity) quinoa (Chenopodium quinoa Willd.) plants was assessed. During the current study two cultivars of quinoa (V7 and V9) were used. This study revealed that water stress adversely affects the fresh and dry weight of shoots and roots as well as chlorophyll pigments (a and b) of both quinoa cultivars. In contrast, drought stress enhanced glycinebetaine (GB), free proline, phenolic content, hydrogen peroxide (H₂O₂), activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzymes, and relative membrane permeability (RMP). However, application of neem leaf extract improved the accumulation of key osmoprotectants like proline, GB and activities of enzymatic antioxidants. Our findings showed 5 % neem leaf extract is an effective treatment in counteracting the oxidative damage caused by water stress, thereby improving overall plant growth. Of both cultivars of quinoa, the response of cv. V9 to stress as well as foliar applied neem was relatively more promising.