Phytochemical and pharmacological validation of folklore medicine practiced in south-western Satpuda Ranges (India) for management of inflammatory conditions.

INTRODUCTION: The ethnobotanical survey of the South-western Satpuda ranges has continued for decades. However, very few disease-specific surveys and their pharmacological validation have been published. The present study aimed to identify, document, and pharmacologically validate the tribal knowledge on anti-inflammatory medicinal plants. METHODS: The field survey was conducted over a year from July 2015 to June 2016, scattered in the South-Western region of Satpuda Ranges. Documentation and identification of the medicinal herbs used often in the treatment of inflammatory conditions. Two plants, namely Eulophia herbacea Lindl., and Grewia flavescens A. Juss. were commonly used for inflammatory conditions. Phytopharmacological validation was done using carrageenan induced inflammation and CFA-induced arthritis. RESULTS: The current investigation identified 32 plants from 22 different families as anti-inflammatory plants. G. flavescens exhibited substantial antiarthritic action in complete Freund's adjuvant-induced arthritis in rats, and E. herbacea showed powerful anti-inflammatory activity in carrageenan-induced rat paw edema model. This activity might be attributed to the presence of gallic acid, quercetin, ß-sitosterol and lupeol. CONCLUSION: The research reveals that selected plants had anti-inflammatory properties in both acute and chronic inflammation. Further studies to highlight the exact mechanism of action of these plants are warranted.

Electrostatic deposition assisted preparation, characterization and evaluation of chrysin liposomes for breast cancer treatment.

Chrysin (CHR), a flavone found in multiple vegetables, fruits and mushrooms has been explored so far as a neurotropic, anti-inflammatory and anti-cancer biomolecule. Despite the stated therapeutic potential, low solubility and bioavailability limit its therapeutic benefit. To circumvent these drawbacks, development of chrysin liposomes (CLPs) is reported in the present investigation. The CLPs were developed by electrostatic deposition assisted film hydration method using chitosan/lecithin to protect chrysin in the nano-lipoidal shell. Developed CLPs were extensively characterized by DSC, XPRD, FE-SEM, TEM, particle size, polydispersity index, zeta potential, percent drug loading and encapsulation efficiency. These CLPs were further characterized by in vitro dissolution, in vivo bioavailability, in vitro anticancer and stability study. Suitable particle size, PDI and ZP implying stabilization of developed CLPs. The % DL and % EE was found to be 3.56 ± 0.13 and 90.5 ± 1.49 respectively. DSC and PXRD study revealed amorphous transition of CHR, which may help to increase its solubility and dissolution profile. In vivo pharmacokinetic study demonstrated more than 5-fold increase in relative bioavailability of CLPs. The in silico molecular docking study results demonstrated the electrostatic interaction between two polymers. The present study suggests that chitosan could protect and encapsulate chrysin which eventually enhances its cytotoxicity as well as bioavailability.

Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life.

AIM: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes. METHODS: A 32 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA). The in vivo antidiabetic study was carried on induced diabetic rats. RESULTS: The optimised liquid SMEDDS-HES (OF) formulation showed emulsification time (Y 1) = 102.5 ± 2.52 s, globule size (Y 2) = 225.2 ± 3.40 nm, polydispersity index (Y 3) = 0.294 ± 0.62, and zeta potential (Y 4) = -25.4 ± 1.74 mV, respectively. The solid SMEDDS-HES (SOF-7) formulation was characterised by FTIR, PXRD, DSC, and SEM. The shelf life of SOF-7 was found to be 32.88 months. The heamatological and histopathological data of diabetic rats showed prominent antidiabetic activity. CONCLUSIONS: The optimised formulation showed improved dissolution, desired stability, and promising antidiabetic activity.

Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals.

Inflammation is one of the common events in the majority of acute as well as chronic debilitating diseases and represent a chief cause of morbidity in today's era of modern lifestyle. If unchecked, inflammation leads to development of rheumatoid arthritis, diabetes, cancer, Alzheimer's disease, and atherosclerosis along with pulmonary, autoimmune and cardiovascular diseases. Inflammation involves a complex network of many mediators, a variety of cells, and execution of multiple pathways. Current therapy for inflammatory diseases is limited to the steroidal and non-steroidal anti-inflammatory agents. The chronic use of these drugs is reported to cause severe adverse effects like gastrointestinal, cardiovascular, and renal abnormalities. There is a massive need to explore new anti-inflammatory agents with selective action and lesser toxicity. Plants and isolated phytoconstituents are promising and interesting sources of new anti-inflammatories. However, drug development from natural sources has been linked with hurdles like the complex nature of extracts, difficulties in isolation of pure phytoconstituents, and the yield of isolated compounds in minute quantities that is insufficient for subsequent lead development. Although various in-vivo and in-vitro models for anti-inflammatory drug development are available, judicious selection of appropriate animal models is a vital step in the early phase of drug development. Systematic evaluation of phytoconstituents can facilitate the identification and development of potential anti-inflammatory leads from natural sources. The present review describes various techniques of anti-inflammatory drug screening with its advantages and limitations, elaboration on biological targets of phytoconstituents in inflammation and biomarkers for the prediction of adverse effects of anti-inflammatory drugs. The systematic approach proposed through present article for anti-inflammatory drug screening can rationalize the identification of novel phytoconstituents at the initial stage of drug screening programs.

Evaluation of analgesic and anti-inflammatory activity of Bridelia retusa (Spreng) bark.

Several species of Bridelia have been used in the condition of pain & arthritis in Indian folk medicine. Present study revealed the preliminary phytochemical investigation and evaluation of analgesic, anti-inflammatory and anti-arthritic activity as well as underlying mechanism of bark of Bridelia retusa Spreng. (Euphorbiaceae). The bark was subjected to extraction using pet.ether, ethyl acetate and acetone. All the extracts were significantly inhibit abdominal writhings response and licking time in late phase of formalin test. Extracts could also significantly inhibit mean paw edema of rats induced by carrageenan & histamine at dose of 200 & 400 mg/kg, i.p. Test materials also showed significant dose dependent reduction in cotton pellet granuloma & acetic acid induced vascular permeability at 400 mg/kg. Oral administration of B. retusa fractions in CFA induced arthritic rats, physical, biochemical and hematological parameters observed in arthritic animals were altered significantly to near normal condition. The maximum paw edema inhibition at day 21 was observed at 400 mg/kg. It also proved significant protection against protein denaturation & RBC membrane damage. The GC-MS analysis of EA extract revealed the presence of ß-sitosterol, stigmasterol, lupeol and friedelin (Pentacyclic triterpenoid). Therefore present study has demonstrated the analgesic; anti-inflammatory and anti-arthritic activities of B. retusa bark and suggested that the molecular membrane might be associated with inhibition of biochemical and hematological parameters. Overall bioactive profile of B. retusa used phytomedicine in future for inflammatory conditions.

Ethnomedicinal plants used for snakebite in India: a brief overview.

The result of human interface and assortment of the most desirable, influential, and successful plant species found in the immediate environment at a precise circumstance is attributable to indigenous knowledge of plant species. India has a rich variety of medicinal plants growing under different geographical and ecological conditions; 1500 out of 15,000 privileged plant species have been reported to have medicinal uses. Snakebite is a severe medical, social, and economic problem in many parts of the world, chiefly in tropical and subtropical nations where majority of the world's dangerous snakes are found and where access to treatment is limited. In India, a range of medicinal plants are used as antidotes for snakebites, used either singly or in combination with other agents. The present study makes an effort to assemble information on medicinal plants that are grown and used for snakebite treatment in India. From a range of literature sources, data have been compiled with emphasis on the plants, family, parts used, etc., depending on the availability of information. This paper enumerates 523 plant species belonging to 122 families that act as antidotes against snakebites. We believe this study of herbal antidotes against snake venom is of substantial significance to society.

Hepatoprotective effect of poly herbal formulation against various hepatotoxic agents in rats.

BACKGROUND: Individually Andrographis paniculata Nees. (Acanthaceae), Phyllanthus niruri Linn.(Euphorbiaceae) and Phyllanthus emblica Linn. single plant extracts have been reported to have hepatoprotective activity. However, literature survey shows that no sufficient scientific data has been publish on pharmacological evaluation of these plants in combined form. METHOD: Hepatoprotective activity of the polyherbal hepatoprotaective formulation (PHF)-containing spray-dried aqueous extracts of Andrographis paniculata Nees. (Acanthaceae), Phyllanthus niruri Linn. (Euphorbiaceae) and Phyllanthus emblica Linn. (Euphorbiaceae), was screened against paracetamol, carbon tetrachloride (CCl(4)), and ethanol-induced hepatic damage in rats. PHF was evaluated by measuring levels of serum marker enzymes like SGOT, SGPT, ALP, direct bilirubin (DB), and lactate dehydrogenase (LDH). The histological studies were also studied support the biochemical parameters. Silymarin was used as standard drug. RESULTS: Administration of PHF (100 and 200 mg/kg p.o.) significantly inhibited paracetamol, CCl(4) and ethanol-induced elevation levels of SGPT, SGOT, ALP, DB and LDH. A comparative histopathological study of liver exhibited almost normal architecture as compared to toxicant group. CONCLUSION: Results suggests that the hepatoprotective effects of PHF might be useful for liver protection due to combined action of all plant extracts along with their phytoconstituents.

Amaranthus spinosus Linn. inhibits mast cell-mediated anaphylactic reactions.

The current study characterizes the mechanism by which the Amaranthus spinosus (Amaranthaceae) decreases mast cell-mediated anaphylactic reactions. Anaphylaxis is a typical hypersensitivity Type I reaction, sharing common mechanisms with asthma in its early and late phases. Mast cells are key as effector cells in hypersensitivity Type I reactions. A. spinosus has been traditionally used in the treatment of allergic bronchitis and asthma, but its role in mast cell-mediated anaphylactic reactions has not fully been investigated. This report investigated the potential effects of the ethyl acetate fraction of A. spinosus leaves (EAFAS) against a compound 48/80 (potent secretagogue)-induced systemic anaphylactic shock paradigm in a mouse model. In addition, rat peritoneal mast cells (RPMC) were used in in vitro studies to investigate the effect of EAFAS on compound 48/80-induced peritoneal mast cell degranulation and histamine release. When administration by the oral route-1 h before compound 48/80 injection-EAFAS (at dose from 0.001-1 g/kg) completely inhibited the induced anaphylactic shock. EAFAS at concentrations ranging 0.25-1 mg/ml dose-dependently attenuated rates of mast cell degranulation and histamine release from RPMC that were evoked by compound 48/80. The results of the present investigation indicated that EAFAS stabilizes the mast cell lipid bilayer membrane, thereby preventing the perturbation of membrane and the release of histamine. As a result of these anti-degranulating and anti-histaminic effects, it can be suggested that EAFAS may have a potential use in the prophylaxis and management of anaphylactic reactions.

Pharmacognostic and phytochemical studies on Ficus Microcarpa L. fil.

BACKGROUND: Ficus microcarpa L. fil. (Syn: Ficus retusa) (Moraceae) is well-known traditional medicinal plant. The bark is used for diverse health ailments in traditional and folklore remedies. AIMS: The present study was undertaken to lay down pharmacognostical and phytochemical standards. MATERIALS AND METHODS: Pharmacognostic studies on fresh, dried and powdered bark was carried out to determine it's morphological, anatomical, and phytochemical diagnostic features. Furthermore, major phytoconstituents were identified from the extracts with the help of high performance liquid chromatography (HPLC) study. RESULTS: The morphology showed to be soft, brittle, rough, shallow vertical, irregularly oriented fissures, curved surface; with splintering, laminated fracture. Microscopically F. microcarpa showed all general characteristics of bark with some distinct differentiation. The phellem is thin and even, phelloderm few cell and rectangular and followed by smaller sclerides, the phloem rays are broad, multi-serrate and showed the scattered bundles of sclerides. The fluorescence and physicochemical standards for bark were established. HPLC analysis showed the predominant presence of therapeutically important phytoconstituents such as oleanolic, betulinic acid, lupeol, ß-sitosterol, catechin, and gallic acid. CONCLUSION: The bark of F. microcarpa considered equivalent to other Ficus species, such as Ficus virens, Ficus infectoria, Ficus arnottiana, Ficus lacor, and Ficus talboti. However, there is no pharmacognostical and phytochemical reports on F. microcarpa to authenticate and differentiate it from similar species. Present work has described pharmacognostical and phytochemical characteristics of F. microcarpa and diagnostic features to differentiate it.

Oleanolic acid prevents glucocorticoid-induced hypertension in rats.

The present study was designed to evaluate the antihypertensive activity of oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a probable mechanism of action for this effect. Male Wistar rats (300-350 g) received dexamethasone (20 µg/kg/day s.c.) or saline (vehicle) for 10 days. In a prevention study, the rats received oleanolic acid (60 mg/kg i.p.) for 5 days, followed by dexamethasone or saline for 10 days. During this period the systolic blood pressure and body weight were evaluated on alternate days. At the end of the experiment, the weight of the thymus gland, plasma nitrate/nitrite (nitric oxide metabolites) concentration and cardiac lipid peroxidation value were determined. Oleanolic acid (60 mg/kg i.p.) significantly prevented a rise in the systolic blood pressure and cardiac lipid peroxidation level after administration of dexamethasone (p < 0.01 and p < 0.05, respectively) without showing any significant effect on the dexamethasone-induced change in body and thymus weights. The decrease in concentration of plasma nitrate/nitrite due to dexamethasone was prevented significantly in the group treated with oleanolic acid (p < 0.05). These findings suggest that oleanolic acid (60 mg/kg i.p.) prevents dexamethasone-induced hypertension in rats, which may be attributed to its antioxidant and nitric oxide releasing action.

Free radical scavenging and hepatoprotective potential of Ficus microcarpa L. fil. bark extracts.

Successive extracts of Ficus microcarpa L. fil. bark (FMB) were tested for antioxidant and hepatoprotective activity against carbon tetrachloride- and paracetamol-induced hepatotoxicities in rats. The ethyl acetate extract of FMB exhibited significant antioxidant and hepatoprotective activity by reducing carbon tetrachloride- and paracetamol-induced changes in biochemical parameters as evidenced by enzymatic and histological examination. Pretreatment with ethyl acetate extract of FMB significantly shortened the duration of pentobarbitone-induced necrosis in mice, indicating its hepatoprotective potential. Phytochemical studies confirmed the presence of the phenolic compound, catechin, in FMB, which may interfere with free-radical formation and may account for its significant hepatoprotective effects. The present study thus provides a scientific rationale for the traditional use of this plant in the management of liver disorders.

Hypolipidemic activity of Moringa oleifera Lam., Moringaceae, on high fat diet induced hyperlipidemia in albino rats / Atividade hipolipidemica de Moringa oleifera Lam., Moringaceae, na hiperlipidemia induzida por dieta rica em gordura em ratos albinos

The leaves of Moringa oleifera Lam., Moringaceae, are used by the Indians in their herbal medicine as a hypolipidemic agent in obese patients. Albino Wistar rats were fed with methanolic extract of M. oleifera (150, 300 and 600 mg/kg, p.o.) and simvastatin (4 mg/kg, p.o.) along with hyperlipidemic diet for 30 days. Moringa oleifera and simvastatin were found to lower the serum cholesterol, triacylglyceride, VLDL, LDL, and atherogenic index, but were found to increase the HDL as compared to the corresponding high fed cholesterol diet group (control). The Moringa oleifera methanolic extract was also investigated for its mechanism of action by estimating HMG CO-A reductase activity. Moringa oleifera was found to increase the excretion of fecal cholesterol. Thus, the study demonstrates that M. oleifera possesses a hypolipidemic effect.

As folhas de Moringa oleifera Lam., Moringaceae, são usados na medicina natural da Índia como um agente hipolipemiante em pacientes obesos. Ratos albinos Wistar foram alimentados com extrato metanólico de M. oleifera (150, 300 e 600 mg/kg, p.o.) e sinvastatina (4 mg/kg, p.o.), juntamente com dieta hiperlipídica por 30 dias. Moringa oleifera e sinvastatina reduziram o colesterol, triacilglicerídeoss, VLDL, LDL e índice aterogênico, mas não aumentaram o HDL em comparação com o grupo controle, com dieta rica em colesterol. O mecanismo de ação do extrato metanólico de Moringa oleifera foi também investigado estimando atividade de HMG CO-A redutase. Moringa oleifera aumentou a excreção fecal de colesterol. Assim, o estudo demonstra que a M. oleifera parece ter efeito hipolipemiante.

Dual effect of Toxicodendron pubescens on Carrageenan induced paw edema in rats.

BACKGROUND: Toxicodendron pubescens is the current botanical name of homeopathic Rhus toxicodendron (Rhus tox). Rhus tox drug is widely used in homeopathically diluted form in the treatment of inflammatory and edematous conditions. We studied the effect of crude form of this plant, after single and multiple doses in Carrageenan induced paw inflammation in rats. METHOD: We evaluated effects of single dose and multiple doses of orally administered Rhus tox on Carrageenan induced paw inflammation in rats. We tested 10 mg/kg, 20 mg/kg and 40 mg/kg doses of Rhus tox. In the single dose study, Rhus tox was administered 1 h prior to the subplantar injection of Carrageenan. In the multiple dose study, Rhus tox was administered twice daily for three days and Carrageenan was injected 1 h after the last dose. Paw volume was measured using a digital plethysmometer. RESULTS: Administration of a single dose of Rhus tox 1h prior to injection of Carrageenan significantly reduced the paw inflammation in a dose dependent manner. Administration of multiple doses of Rhus tox increased the intensity of inflammation induced by Carrageenan, but this was not statistically significant. CONCLUSION: Rhus tox, in crude form, exerts anti-inflammatory effects after a single dose and proinflammatory effect after multiple doses in Carrageenan induced paw inflammation in rats. Further study is needed to explain this dual effect.