Antifilarial Activity Research Articles

An Overview on Antifilarial Efficacy of Heterocyclic Motifs Encompassing Synthetic Strategies, SAR, and Commercialized Medications.

Filariasis is one of the oldest, most dangerous, debilitating, disfiguring diseases and often ignores tropical disorders. It presents with a range of clinical symptoms, a low death rate, and a high morbidity rate, which contributes to social discrimination. This condition has major effects on people's socioeconomic circumstances. This illness is carried by mosquitoes that have spread malaria. Lymphatic filariasis, caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori, is a crippling illness with serious social and economic consequences. The infection persisted despite therapy with conventional antifilarial medications such as diethylcarbamazine (DEC), albendazole, and ivermectin, which are mostly microfilaricides. Current treatments (ivermectin, diethylcarbamazine, and albendazole) have limited effectiveness against adult parasites and produce side effects; therefore, innovative antifilarial medications are urgently required. Hence, macrofilaricides, embryostatic agents, and improved microfilaricides are required. The following article discusses the typical synthetic methodologies established for antifilarial activity as well as their marketed pharmaceuticals, which will help researchers, medicinal chemists, and pharmaceutical scientists to develop new and effective antifilarial therapies. This review can help to identify new lead compounds and optimize existing commercial medications to improve their therapeutic efficacy. The majority of the studies addressed in this review concern the forms of filariasis, parasite life cycle, symptoms, medications used to treat filariasis, synthetic schemes, SAR, and results from the reported research.

Exploring the Pharmacological Potential of Acacia auriculiformis: A Comprehensive Review of Medicinal Properties and Therapeutic Applications

This review explores the pharmacological potential of Acacia auriculiformis, highlighting its diverse medicinal properties and therapeutic applications. Through a detailed analysis of experimental evidence, the study showcases the plant's efficacy in various health concerns. The plant exhibits significant wound healing, antifungal, antibacterial, antifilarial, antioxidant, antimalarial, hepatoprotective, chemoprotective, antimutagenic, CNS depressant, spermicidal, and cestocidal activities. The global interest in herbal medicine and the increasing utilization of A. auriculiformis underscore its importance in alternative healthcare approaches. The review emphasizes the need for further research to elucidate the mechanisms of action underlying the plant's pharmacological activities and to explore its potential clinical benefits. The findings suggest that A. auriculiformis holds promise as a source of therapeutic agents for a wide range of health conditions. Continued investigation into the bioactive compounds derived from the plant, along with clinical trials to assess efficacy and safety, could pave the way for the development of novel treatments. Overall, this review sheds light on the multifaceted medicinal properties of A. auriculiformis and its potential contribution to the field of herbal medicine and drug discovery.

In Vitro Filaricidal Properties of Aqueous Extracts of Combretum nigricans (Combretaceae) on Onchocerca ochengi (Onchocercidae).

Onchocerciasis is an endemic parasitic disease in sub-Saharan Africa that significantly impacts animal and human health. In Northern Cameroon, medicinal plants from the Combretum genus are used for onchocerciasis traditional treatment although there is no scientific evidence of their antifilarial potential. This study evaluates the in vitro macro- and microfilaricidal properties of water extracts from Combretum nigricans in Onchocerca ochengi. Material and Methods. O. ochengi microfilariae and adult male worms were recovered from cowhide fragments. Oxidative stress indicators and motility tests were used to assess the filaricidal impact. Female albino rats were used to test for acute toxicity. The contents of secondary metabolites were quantified. The bark aqueous extract was more active on macrofilariae at 1 mg/mL for 24 h (100%) than the leaf (63.9%) and root (75%) extracts at the same concentration. Likewise, a stronger microfilaricidal effect was found with this extract at 0.5 mg/mL for 1 h (100%) compared to root and leaf extracts. The dose-response effect with the bark extract gave an inhibitory concentration 50 (IC50) of 351 μg/mL vs. 113 μg/mL for flubendazole after 24 h incubation, while the microfilaricidal efficacy revealed an IC50 of 158.7 μg/mL vs. 54.09 μg/mL for ivermectin after one-hour incubation. Examining stress indicators on parasite homogenates showed that macrofilaricidal activity is associated with a significant increase in nitric oxide, glutathione, and malondialdehyde generation and a decrease in catalase activity. At 2000 mg/kg, rats showed no harm. The phytochemical investigation revealed that the barks contained more phenolic acids, condensed tannins, flavonoids, and saponins than the leaves (p < 0.001). These findings support C. nigricans' antifilarial activity and identify oxidative stress indicators as prospective treatment targets in O. ochengi. It would be interesting to conduct in vivo studies to understand their antifilarial activity better.

Anthelmintic and anti-filarial coumarins of natural and synthetic origin: Chemical and biological intervention

Coumarin is a bicyclic system with a lactone-(hetero)aryl motif and a critical structural unit of many natural and synthetic pharmaceutical compounds. The coumarins possess a broad spectrum of biological activities and have successful clinical applications. Several coumarin-based natural compounds like osthol, isopimpinellin, umbelliferon, scopoletin, scopoline, cleomiscosin A to D, and inophyllum E have been isolated with anthelmintic and antifilarial activities. The ability of coumarin to interact with various active sites through noncovalent interactions like van der Waals forces, metal coordination, electrostatic and hydrophobic interaction, as well as hydrogen bonding, have led to the synthesis of different coumarins with significant anthelmintic and anti-filarial activities. The SAR studies of parasitic coumarins revealed that a hydroxy group at C-4 and C-7 positions has a deciding role in the anthelmintic and anti-filarial activity. The careful structure–activity studies could be effectively employed in the structural optimization of the bicyclic coumarin ring, allowing it to have many derivatives that could be screened for helminthiases. We hope this review will provide a structure-based input to researchers to design and develop novel coumarin hybrids to treat helminthiasis and filariasis.

Biosynthesis and characterization of Ocimum sanctum green silver nanoparticles and unravelling their enhanced anti-filarial activity through a HRAMS proteomics approach.

The available anti-filarial medications are largely ineffective against adult filarial worms. Also, these drugs have several drawbacks such as toxicity and development of resistance owing to long-term usage. Green nanomedicine may offer better solutions for Lymphatic Filariasis treatment due to its tiny size, biocompatibility, and better penetration at considerably lower costs with higher therapeutic efficacy. In the present study, Ocimum sanctum silver nanoparticles (OSAgNPs) were bio-synthesized and their anti-filarial efficacy was evaluated against adult filarial parasites. The green nanoparticles were characterized by UV-VIS spectroscopy, XRD, FTIR, SEM, and TEM analysis. The OSAgNPs significantly affected the motility and viability of adult Setaria cervi parasites after 4 h of incubation at concentrations higher than 0.5 μg ml-1. Proteomics analysis by high resolution accurate mass spectrometry revealed that 213 proteins were differentially expressed following OSAgNP treatment. Mostly these DEPs belonged to the many biochemical and molecular pathways of parasites such as muscle proteins, antioxidant proteins, heat shock proteins, signal recognition proteins, and energy metabolism-related proteins. Undoubtedly, this study will open new avenues for the development of novel anti-filarial drugs based on green nanoparticles.

Anti-filarial efficacy of Centratherum anthelminticum: unravelling the underlying mechanisms through biochemical, HRAMS proteomics and MD simulation approaches.

Traditionally, Centratherum anthelminticum (CA) has been reported to be a potent anti-filarial, however no reports are available detailing its mechanism of action against filarial parasites. In this study, we have evaluated the anti-filarial activity of CA against lymphatic filarial parasites Setaria cervi using ex vivo biochemical, proteomics and in silico approaches. The motility and viability of the parasites decreased significantly after treatment with CA concentrations of ≥125 μg mL-1. An increase in lipid peroxidation (51.92%), protein carbonylation (48.99%), NADPH oxidase (88.88%) activity and decrease in the glutathione (GSH) (-39.23%), glutathione reductase (GR) (-60.17%), and glutathione S-transferase (GST) (-50.48%) activity was also observed after CA treatment. The proteomics analysis was performed by two-dimensional gel electrophoresis and high-resolution accurate mass spectrometry (HRAMS). In total, 185 proteins were differentially expressed (DEPs) following CA treatment. The major DEPs were mostly involved in tRNA processing, biosynthetic processes, metabolic activities, protein transport, the tricarboxylic acid cycle, protein translation, and stress response. The UPLC-ESI-MS/MS analysis of CA extract revealed the presence of 40 bioactive compounds. Further the docking analysis showed 10 CA bioactive compounds to have high binding affinity towards antioxidant proteins of filarial parasites. Additionally, MD simulation studies showed stable interactions (RMSF ≤ 10 Å) of 3-O-methylquercitin, quinic acid, gentisic acid, and vanillin with filarial antioxidant enzymes/proteins. To our knowledge, this is the first report detailing the molecular mechanism of anti-filarial activity of CA, which can be further evaluated for the development of new anti-filarial formulations.

Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review.

The incorporation of heterocyclic moieties into the standard chemical structure with a biologically active scaffold has become of crucial practice for the construction of pharmacologically potent candidates in the drug arena. Currently, numerous kinds of chalcones and their derivatives have been synthesized using the incorporation of heterocyclic scaffolds, especially chalcones bearing heterocyclic moieties that display improved efficiency and potential for drug production in pharmaceutical sectors. The current Review focuses on recent advances in the synthetic approaches and pharmacological activities such as antibacterial, antifungal, antitubercular, antioxidant, antimalarial, anticancer, anti-inflammatory, antigiardial, and antifilarial activities of chalcone derivatives incorporating N-heterocyclic moieties at either the A-ring or B-ring.

In Vitro and In Silico Studies of Glycyrrhetinic Acid Derivatives as Antitubercular Agents

Background: Glycyrrhetinic acid (GA) is a biologically active triterpenoid acid, isolated from the root of the Glycyrrhiza plant species. In our earlier studies, the semisynthetic analogs of GA have been reported to possess improved anticancer activities against various cell lines, antimalarial, and antifilarial activities. Method: GA was isolated and characterized from roots of Glycyrrhiza glabra and converted to its various C-3 aryl ester derivatives via the protection of C-30 carboxylic group. Antitubercular activity was determined against Mycobacterium tuberculosis H37Ra by Agar dilution assay. The in-silico docking was performed for the most active analogue against three antitubercular targets, catalase peroxidase, dihydrofolate reductase and enoyl-ACP reductase. Results: The derivatives, Methyl glycyrrhetinate (GA-1), 3-O-(4-methyl-phenyl)-ethanoyl methyl glycyrrhetinate (GA-1a), 3-O-(4-fluoro phenyl)-ethanoyl methyl glycyrrhetinate (GA-1c), 3-O-(4-methoxy trans cinnamyl)-ethanoyl methyl glycyrrhetinate (GA-1e) and 3-O-{(4-chlorophenyl)-ethanoyl methyl glycyrrhetinate (GA-1g) showed improved antitubercular activity (in the range 38.76 to 51.546 mM) over the parent molecule (MIC &gt;106.157 mM). The derivative, 3-O-(4-aminobenzoyl)- methyl glycyrrhetinate (GA-1h) was found most active (MIC 20.695 mM) which was further supported by high binding affinity with the selected antitubercular target proteins in in silico docking studies. Conclusion: Synthetic modifications on GA led to C-3 aryl ester derivatives with improved antitubercular activities. Further studies for the development of GA-1h as potential antitubercular lead is therefore warranted.

Review on Medicinal Importance of Butea monosperma Lam. (Taub)

Butea monosperma is a renowned therapeutic plant, a medium size deciduous tree broadly dispersed in India, Bangladesh, Cambodia, Myanmar, China South-Central, Nepal, Laos, Sri Lanka, China Southeast, Pakistan, and Vietnam. Butea monosperma is being used in customary medication preparation from the pre historic period. It is acknowledged as the forest’s flame and is often branded as Dhak or Palash. It is described in Upanishads, Susruta Samhita, Vedas, Ashtanga Sangraha, Astanga Hridaya, and Charka Samhita. It belongs to the family of Fabaceae, which has an extensive range of vigorous principles, and it has phytoconstituents such as glycosides, flavonoids, etc.This revisional analysis is focused on the pharmacological actions, mainly shown by seeds, flowers, fruits, barks,leaves, etc., like anti-diabetic, anthelmintic, hepatoprotective, anti-stress, anti-implantation, anti-convulsant, wound healing, giardiasis, anti-oxidant, anti-dopaminergic, anti-microbial, sunscreen, anti-diarrheal, free radical scavenging, anti-filarial, anti-fungal, nephroprotective, protease inhibitor, osteogenic, hemagglutinating, anti-ulcer, giardiasis, anti-asthmatic, anti-inflammatory, anti-fertility and anti-cancer activity. GC-MS analysis of Butea monospermashows the attendance of important compounds which is volatile and HPLC analysis for non-volatile, which supplies light to its medicinal properties. These therapeutic chattels may provide impending active principles with advanced usefulness and the leastafter-effects as equated to accessible artificial drugs.

Michael Adduct of Sulfonamide Chalcone Targets Folate Metabolism in Brugia Malayi Parasite

A series of Michael adducts of malononitrile and sulfonamide chalcones were synthesized, characterized, and evaluated for their antifilarial activity. Out of 14 compounds, N-(4-(4,4-dicyano-3-p-tolylbutanoyl)phenyl)benzenesulfonamide showed favorable drug-likeness properties with marked antifilarial effects at micro-molar dosages. Apoptosis in Brugia malayi microfilariae was confirmed by EB/AO staining, MTT assay, and cytoplasmic cytochrome c ELISA. Since chalcone and folate synthesis pathways share the same substrate, we hypothesize a structural analogy-based inhibition of folate metabolism by this compound. Molecular docking against a pre-validated BmDHFR protein showed more favorable thermodynamic parameters than a positive control, epicatechin-3-gallate. The compound significantly suppressed the DHFR activity in a parasite extract in vitro. Our hypothesis is also supported by a significant reversal of DHFR inhibition by folate addition, which indicated a plausible mechanism of competitive inhibition. These results demonstrate that targeting filarial folate metabolism through DHFR with consequent apoptosis induction might be rewarding for therapeutic intervention. This study reveals a novel rationale of the structural analogy-based competitive inhibition of DHFR by Michael adducts of sulfonamide chalcones.

Deciphering the anti-filarial potential of bioactive compounds from Ocimum sanctum: a combined experimental and computational study

Context The anthelminthic effect of Ocimum species (Lamiaceae) has been reported, however, its anti-filarial effect has not been explored to date. Objective This study evaluates the effect of Ocimum sanctum L. (OS) against lymphatic filarial parasites. Material and methods The ethanol extract of OS (EOS) leaves was tested for anti-filarial activity against Setaria cervi. Equal size and number (n = 10) of adult female S. cervi worms were incubated in 125, 250 or 375 μg/mL EOS extract for 6 h at 37 °C. The OS bioactive components were identified by UPLC-ESI-MS/MS and subjected to docking and molecular dynamics (MD) simulation against filarial antioxidant proteins. Results The EOS significantly inhibited the motility of adult female S. cervi after 6 h of incubation. The motility was found to be reduced by 53.7% in 375 µg/mL and 43.8% in 250 µg/mL EOS after 6 h of treatment. The UPLC-ESI-MS/MS analysis of ethanol extract of O. sanctum revealed the presence of 13 bioactive compounds. The docking analysis showed eight OS bioactive compounds to have high binding affinity (> 4.8 kcal/mol) towards antioxidant proteins of filarial parasites. Additionally, MD simulation studies showed significant impact of (RMSD ≤ 10 Å) chlorogenic acid, luteolin and ursolic acid on filarial antioxidant enzymes/proteins. To our knowledge, this is the first report of the anti-filarial activity of Ocimum sanctum. Discussion and conclusions The effect of EOS and OS bioactive components on human filarial parasites can be further evaluated for the development of new anti-filarial formulations.

Pharmacotherapeutics Applications and Chemistry of Chalcone Derivatives.

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,β-unsaturated system in the chalcone’s rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.

Antifilarial Activity of the Methanolic Extract of Indigofera tinctoria (Fabaceae) on Bovine Parasites (Onchocerca ochengi).

Onchocerciasis is a major public health problem caused by Onchocerca volvulus parasite and transmitted to humans via black flies (simulium) bites. The control of onchocerciasis relies much on the use of the chemical drug ivermectin, which is only effective against microfilariae and has led to drug resistance. This study was carried out to assess the in vitro antifilarial activity of methanolic extract of Indigofera tinctoria and its most active fractions on adult male O. ochengi worm, the closest model to O. volvulus, after 48 h and 72 h of treatment. Worms' viability was determined biochemically by MTT/formazan colorimetry assay. The promising plant extract's acute and subacute oral toxicity were evaluated on both mice and rats. The result revealed a highest antifilarial activity of the methanolic extract (LC50 = 12.28 μg/mL) compared to ivermectin (LC50 = 26.50 μg/mL) after 72 h of treatment. Out of the eight (08), chromatographic fractions screened, only three (03) fractions (C, F, and G) revealed the highest anti-Onchocerca activity after 72 h of treatment. An oral administration of the plant extract at a single dose of 2000 mg/kg did not produce any toxicity in mice. After repeated daily administration of methanolic extract of I. tinctoria (250 mg/kg, 500 mg/kg, and 1000 mg/kg) for 28 days, no significant changes in body weight, biochemical, and haematological parameters was observed. Histopathological examination of organs did not reveal any sign of alteration. The phytochemical analysis of the methanolic extract of I. tinctoria revealed the presence of various phenolic compounds. Therefore, this study demonstrated the potential antifilarial activity of Indigofera tinctoria and offered an alternative to treating onchocerciasis. Moreover, further studies could be developed in promising new antifilarial sources of the isolated compound and in vivo antifilarial activity of Indigofera tinctoria in the animal model needs to be studied.

Antifilarial efficacy of andrographolide: Ex vivo studies on bovine filarial parasite Setaria cervi

Lymphatic filariasis caused by filarial nematode is an important disease leading to considerable morbidity throughout tropical countries. Even after specific elimination programs, the disease continue to spread in endemic countries. Thus newer therapeutic interventions are urgently needed to control the spread. In the present study, we have seen the effect of andrographolide (andro), a diterpenoid lactone from the leaves of Andrographis paniculata on filarial parasite Setaria cervi. There was time and concentration dependent decrease in motility and viability leading to death of parasite after 6 h of the exposure of andro. Andro showed potential antifilarial activity with an IC50 value of 24.80 μM assessed through MTT assay. There was concentration dependent decrease in the antioxidant enzymes activity and increase in proapoptotic markers after 5 h exposure of andro. Further, molecular docking analysis revealed that andro binds with filarial glutathione-S-transferase at glutathione (GSH) binding site and inhibiting enzyme activity competitively. Andro induced oxidative stress mediated apoptosis in parasites as evidenced by increase in the intracellular reactive oxygen species (ROS) and apoptotic markers.Therefore this study suggested that andro could be further explored as a new antifilarial drug.

Phytopharmaceutical and pharmacological aspects of “pongamia pinnata”-a comprehensive review

In the last few decades the importance of medicinal plant and its vitality in modern medicine has played a pivotal role in drug discovery and its development. The vast novelty, efficacy and least side effects of the plants have gained the attraction of the researchers, which has led to the exploitation of many traditional medicinal plants and herbs for their therapeutical activities. Even through these efforts there are still some traditional plants that are yet to be exploited for their therapeutic significance, one of such prominent plants is Pongamia pinnata. The plant shows diverse pharmacological activities due to presence of many primary and secondary metabolites. This diversity of many phytoconstituents like alkaloids, flavonoids, tannins, glycosides and other which may be the reason for its pharmacological activities which include wound healing, anti-inflammatory, antibacterial, anti-ulcer, anti-filarial, anti-diabetic and other activities. The present study is an effort to compile all the available details regarding the characteristics of the plant species, phytoconstituents, traditional use, pharmacological uses and research undertaken related to P. pinnata.

Antifilarial Screening and Oxidative Role of Isolated Fraction from Aegle Marmelos Corr. Leaves Extract

In the present work antifilarial active fraction was isolated from the leaves Chloroform extract of Aegle marmelos Corr. evaluated in vitro for antifilarial activity and studied the possible oxidative role against Setaria cervi parasite. Antifilarial study was carried out with isolated fractions by worm motility and MTT assays. Complete parasite motility inhibition was observed at 0.002 to 0.08 mg/mL in motility assay and in MTT assay plant fraction gave &gt; 50% reduction 58.9, 74.6 and 97.2% at concentrations 0.02, 0.04 and 0.08 mg/mL at 10, 6 and 2 hours incubation period respectively (p&lt; 0.05). Inhibitory concentration (IC50) was found to be 0.015 mg/mL. Oxidative parameters levels for MDA, Carbonyl content and Nitric oxide were identified as antifilarial activity achieved. The level of oxidative parameters was calculated in dose dependent manners as compared to the control level. The antifilarial activity of isolated fraction is associated with the oxidative mechanism in this study.

Biochemical characterization of Recombinase A from Wolbachia endosymbiont of filarial nematode Brugia malayi (wBmRecA)

Lymphatic filariasis is a debilitating disease that affects over 890 million people in 49 countries. A lack of vaccines, non-availability of adulticidal drugs, the threat of emerging drug resistance against available chemotherapeutics and an incomplete understanding of the immunobiology of the disease have sustained the problem. Characterization of Wolbachia proteins, the bacterial endosymbiont which helps in the growth and development of filarial worms, regulates fecundity in female worms and mediates immunopathogenesis of Lymphatic Filariasis, is an important approach to gain insights into the immunopathogenesis of the disease. In this study, we carried out extensive biochemical characterization of Recombinase A from Wolbachia of the filarial nematode Brugia malayi (wBmRecA) using an Electrophoretic Mobility Shift Assay, an ATP binding and hydrolysis assay, DNA strand exchange reactions, DAPI displacement assay and confocal microscopy, and evaluated anti-filarial activity of RecA inhibitors. Confocal studies showed that wBmRecA was expressed and localised within B. malayi microfilariae (Mf) and uteri and lateral chord of adult females. Recombinant wBmRecA was biochemically active and showed intrinsic binding capacity towards both single-stranded DNA and double-stranded DNA that were enhanced by ATP, suggesting ATP-induced cooperativity. wBmRecA promoted ATP hydrolysis and DNA strand exchange reactions in a concentration-dependent manner, and its binding to DNA was sensitive to temperature, pH and salt concentration. Importantly, the anti-parasitic drug Suramin, and Phthalocyanine tetrasulfonate (PcTs)-based inhibitors Fe-PcTs and 3,4-Cu-PcTs, inhibited wBmRecA activity and affected the motility and viability of Mf. The addition of Doxycycline further enhanced microfilaricidal activity of wBmRecA, suggesting potential synergism. Taken together, the omnipresence of wBmRecA in B. malayi life stages and the potent microfilaricidal activity of RecA inhibitors suggest an important role of wBmRecA in filarial pathogenesis.

Medicinal Potential and Scientific Validations of Mallotus philippinensis (Lam.) Muell. Arg. (Kampillaka): A Review

Mallotus philippinensis (Lam.) M Arg is one of the endangered plants in the central ecoregion. It belongs to the Euphorbiaceae family. Mallotus philippinensis (Lam.) Muell. Arg. (Family: Euphorbiaceae) is a medicinally important common perennial shrub used in indigenous medicine. It is distributed mainly in the tropical and subtropical regions of the world. Though it is a drug of herbal origin, it has been grouped into one of the eight Sadharana rasa groups [Glands and hairs of Mallotus philippinensis (Kampillaka), Arsenic (Somala), Ammonium Chloride (Navasagara), Cowri (Kaparda), Amber (Agnijaara), Red Oxide of Mercury (Girisindoora), Cinnabar (Hingula), Litharge (Muddaarashringa)] in Rasa-shastra (Ayurveda study of minerals and metals) of Ayurvedic pharmacopoeia. M. philippinensis is included in Virecana ghana (group of medicinal plants or products use to purgation therapy) of Ayurveda medicine. Especially roots, fruits (also as fruit powder) and the leaves are used for medicinal purposes. Leaves are bitter and have a cooling and appetizing nature. The glands/hairs of the fruit and the leaves are recommended for dermal problems. So far, scientific studies have been carried out to prove and look-into the pharmacological activities of M. philippinensis. Here, an attempt is taken to summarize the distribution, morphology, Ayurveda and traditional uses, and scientific investigations on M. philippinensis. Researchers have scientifically proven the Antimicrobial activity, Hepatoprotective activity, Anti-Leukemic activity, Anti-HIV activity, Anti-inflammatory activity, Anti-filarial activity, Analgesic and hypnotic activity, Antiproliferative activity, Antifertility activity, Purgative activity and Anthelmintic activity and Antiallergic activity against different parts of the M. philippinensis.

Pachypodostyflavone, a New 3-methoxy Flavone and Other Constituents with Antifilarial Activities from the Stem Bark of Duguetia staudtii

AbstractA new flavone derivative named pachypodostyflavone (1), along with 8 known compounds (2–9) and a mixture of β-sitosterol and stigmasterol were isolated from the stem bark of Duguetia staudtii (Annonaceae), based on a bioassay-guided fractionation. Their structures were determined using high-resolution mass spectrometry and NMR spectroscopic data, as well as by comparison with the literature values of their analogs. Selected isolated compounds were evaluated for their in vitro antifilaricidal activities on Onchocerca ochengi microfilariae and adult worms. Inhibition of motility was evaluated spectroscopically on microfilaria and adult male worms. Viability was determined on adult female worms by the MTT/ Formazan assay. Auranofin at 10 µM and 2% DMSO were used as positive and negative controls, respectively. Compounds 1 and 7 showed potent anti-onchocerca activities with 100% activity at 250 µg/mL on both O. ochengi adult male and female worms, while compound 5 displayed 100% activity at 30 µg/mL.

Disruption of redox homeostasis with synchronized activation of apoptosis highlights the antifilarial efficacy of novel piperine derivatives: An in vitro mechanistic approach

A series of novel piperine derivatives were synthesized with high yield and were evaluated for its antifilarial potential against the bovine filarial parasite Setaria cervi. Among 21 (3a-3u) compounds screened, three of them (3k, 3l, 3s) showed significant potential against all the developmental stages (oocytes, microfilariae and adult) of the filarial worm in time and dose dependent manner. 3l showed the highest efficacy among the selected three compounds. These three compounds were further evaluated for both in vitro and in vivo toxicity analyses which further fortified the benign nature of the selected compounds. The antifilarial activities they exhibited were clearly fuelled through disparity of the internal redox homeostasis as evidenced from the alterations in the enzymatic and non-enzymatic antioxidants level which ultimately shifted towards activation of pro-apoptotic signaling cascade eventually leading to the death of the parasites. The ability of the compound 3l to bind thioredoxin reductase and CED-3 protein are the key findings of this study. The present study supported with several biological experiments is therefore a maiden report on the antifilarial effectiveness of these novel piperine derivatives.