Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies.

Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties. Aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts of G. tiliaefolia was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, total antioxidant capacity (TAC) assay, reducing power assay (RPA) and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic (TPC) and total flavonoid content (TFC). As revealed by in vitro assays, methanol extract was found to contain more phenolic content. Hence, the methanol extract was further explored for its anticonvulsant potential in pentylenetetrazole (PTZ) induced acute seizures in mice. The methanol extract (400 mg/kg) significantly increased the latency to occurrence of myoclonic jerks and generalized tonic clonic seizures (GTCS). Additionally, it also reduced duration and seizure severity score associated with GTCS. The Grewia tiliaefolia methanol extract was further screened by Ultra High-Performance Liquid Chromatography (UHPLC) for presence of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analysed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3- hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu-AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction for GABA receptor and antagonistic interaction for Glu-AMPA receptor. We concluded that G. tiliaefolia showed anticonvulsant potential possibly because of gallic acid and kaempferol possibly mediated through GABA and Glu-AMPA receptor.

Gut microbiota and Autism Spectrum Disorder: From pathogenesis to potential therapeutic perspectives.

Autism is a complex neurodevelopmental disorder which disrupts communication, social and interactive skills followed by appearance of repetitive behavior. The underlying etiology remains incomprehensible but genetic and environmental factors play a key role. Accumulated evidence shows that alteration in level of gut microbes and their metabolites are not only linked to gastrointestinal problems but also to autism. So far the mix of microbes that is present in the gut affects human health in numerous ways through extensive bacterial-mammalian cometabolism and has a marked influence over health via gut-brain-microbial interactions. Healthy microbiota may even ease the symptoms of autism, as microbial balance influences brain development through the neuroendocrine, neuroimmune, and autonomic nervous systems. In this article, we focused on reviewing the correlation between gut microbiota and their metabolites on symptoms of autism by utilizing prebiotics, probiotics and herbal remedies to target gut microflora hence autism.

Therapeutic and cosmeceutical role of glycosylated natural products in dermatology.

Natural products (NPs) remain the primary source of pharmacologically active candidates for drug discovery. Since time immemorial, NPs have attracted considerable attention because of their beneficial skin effects. Moreover, there has been a great interest in using such products for the cosmetics industry in the past few decades, bridging the gap between modern and traditional medicine. Terpenoids, Steroids, and Flavonoids having glycosidic attachment have proven biological effects with a positive impact on human health. NPs derived glycosides are mainly found in fruits, vegetables, and plants, and most of them have a special reverence in traditional and modern medicine for disease prevention and treatment. A literature review was performed using scientific journals, Google scholar, Scifinder, PubMED, and Google patents. These scientific articles, documents, and patents establish the significance of glycosidic NPs in the areas of dermatology. Considering the human inclination to the usage of NPs rather than synthetic or inorganic drugs (especially in the area of skin care), in the present review we have discussed the worth of NP glycosides in beauty care and skin-related therapeutics and the mechanistic pathways involved.

Neuroprotective activity of novel phenanthrene derivative from Grewia tiliaefolia by in vitro and in silico studies.

Medicinal plants possess range of phytochemicals accountable for their diverse biological activities. Presently, such compounds have been isolated from medicinal plants, characterized and evaluated for their pharmacological potential. In the present study, the efforts have been made to isolate the compound(s) from Grewia tiliaefolia Vahl., plant known for its ameliorative effect on brain related diseases such as anxiety, depression, cognitive disorders and Parkinson's disease. Plant extract was subjected to isolation of compound(s) using column chromatography and isolated compound was characterized by NMR FTIR and LCMS. The isolated compound was novel with the IUPAC name of the compound is propyl 3-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylate, designated as A-1 and has not been reported before. A-1 was further evaluated for its antioxidant potential using in vitro antioxidant assays (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH assay and reducing power assay, RPA). Also, Acetylcholinesterase (AChE) inhibitory potential of A-1 and extract was analysed. Results showed that A-1 exhibited significantly higher antioxidant activity in both DPPH and RPA assay as compared to plant extract. In case of AChE inhibitory activity again, A-1 has shown significantly higher activity as compared to plant extract. In silico study was conducted to predict its action on proteins playing crucial role in neurological and neurodegenerative disorders such as gamma amino butyric acid (GABA) receptor and glutamate α amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu AMPA) receptor in epilepsy and AChE enzyme in Alzheimer's diseases. The compound has shown interaction in following order: AChE > GABA receptor > Glu AMPA receptor. Further, molecular dynamic simulations and ADME studies of A-1 and AChE enzyme revealed that A-1 yielded good results in all parameters and hence can relieve Alzheimer's like symptoms.

Pharmacological and analytical aspects of alkannin/shikonin and their derivatives: An update from 2008 to 2022.

Alkannin/shikonin (A/S) and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants. They are integral constituents of traditional Chinese medicine Zicao (roots of Lithospermum erythrorhizon). In last two decades significant increase in pharmacological investigations on alkannin/shikonin and their derivatives has been reported that resulted in discovery of their novel mechanisms in various diseases and disorders. This review throws light on recently conducted pharmacological investigations on alkannin/shikonin and their derivatives and their outputs. Various analytical aspects are also discussed and brief summary of patent applications on inventions containing alkannin/shikonin and its derivatives is also provided.

Protective effect of Grewia asiatica leaves extract in animal models of epilepsy and anxiety.

Grewia asiatica Linn. is a well-known plant for its nutritional and therapeutic attributes. It has been mentioned in ancient Indian literature as Rasayana due to its stimulant and tonic effects. Thus, present investigation was carried out to evaluate the antiepileptic and anxiolytic action of G. asiatica Linn. leaves using animal models. Methanol extract at dose levels of 100 and 200 mg/kg was capable of providing protection against both pentylenetetrazole and maximal electroshock induced seizures in mice. Extract also showed significant anxiolytic activity in elevated plus maze, light/dark box and mirror chamber mice models at same dose levels. Results of this study indicated that the methanol extract of leaves of G. asiatica plant possess significant antiepileptic and anxiolytic effect.

Protective effect of vanillic acid against diabetes and diabetic nephropathy by attenuating oxidative stress and upregulation of NF-κB, TNF-α and COX-2 proteins in rats.

Diabetes is the most prevalent disorder in the world characterized by uncontrolled high blood glucose levels and nephropathy is one of the chief complications allied with hyperglycemia. Vanillic acid; the main bioactive compound derived from natural sources such as vegetables, fruits and plants possesses various pharmacological activities such as antioxidant, anti-inflammatory and anti-proliferative. The current study was designed to investigate the antidiabetic and renoprotective effects of vanillic acid by its various pharmacological activities. Streptozotocin (50 mg/kg)/nicotinamide (110 mg/kg) was used to induce diabetes in rats. Oral administration of vanillic acid once daily for 6 weeks (25, 50 and 100 mg/kg) significantly reduced the hyperglycemia, increased liver enzymes and normalized lipid profile that was altered in diabetic rats. Moreover, vanillic acid attenuated the impaired renal function as evidenced by a reduction in serum creatinine, urea, uric acid and urinary microproteinuria levels with a concomitant increase in urinary creatinine clearance in the nephropathic rats. Diabetic rats showed a marked increase in thiobarbituric acid reactive substances (TBARS) and superoxide anion generation (SAG) along with decreased reduced glutathione (GSH) in the renal tissue which was ameliorated in the vanillic acid-treated rats. Histopathologically, vanillic acid treatment was associated with reduced damage with normalized structural changes in renal tissue. Furthermore, treatment groups showed the suppression of upregulation of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, cyclo-oxygenase (COX)-2 and up-regulation of Nuclear factor-erythroid 2-related factor 2 (Nrf-2) in the renal tissue. In conclusion, vanillic acid's ameliorative impact on diabetic nephropathic rats may be attributed to its powerful free radical scavenging property, down-regulation of NF-κB, TNF-α, COX-2 and up-regulation of Nrf-2 proteins in renal tissue.

Hepatoprotective effect of Physalis divaricata in paracetamol induced hepatotoxicity: In vitro, in silico and in vivo analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis divaricata D. Don. is an erect weed of family Solanaceae. The root extract of this plant is used by the indigenous communities of Sub-Himalayan region of Uttarakhand, India for the treatment of liver disorders. AIM OF THE STUDY: To evaluate hepatoprotective potential of P. divaricata in paracetamol (PCM) induced hepatotoxicity in rats. MATERIALS AND METHODS: The dried roots of P. divaricata were subjected to extraction using different solvents. The chloroform extract, methanol extract and bioactive aqueous fraction of methanol extract were evaluated for hepatoprotective effect. After initial in vitro screening, all extracts were screened for hepatoprotective potential in PCM (3 g/kg p.o) induced hepatotoxicity. Following PCM administration, extracts were administered orally for 7 days in increasing dose concentrations. All the animals were euthanized on eighth day, serum and liver tissues were collected and subjected to various biochemical and histopathological analysis. Aqueous fraction of methanol extract was further analyzed using LC- MS analysis. RESULTS: Methanol extract and its bioactive aqueous fraction exhibited significant and better in vitro antioxidant and antiproliferative activity as compared to chloroform extract. PCM treatment caused hepatotoxicity as assessed by altered levels of various hepatic biomarkers (increase in the levels of ALT, AST, ALP, albumin, triglycerides, cholesterol, TBARS, and AOPPs as well as decrease in GSH and TrxR levels) along with histopathological changes (portal to portal bridging, necrosis, and inflammation). Methanolic extract (200, 400 and 800 mg/kg) and its aqueous fraction treatment (25, 50 and 100 mg/kg) significantly restored elevated hepatic biomarkers, oxidative stress, and protected normal hepato-architecture. LC-MS analysis of aqueous fraction showed presence of rutin and kaempferol. In silico analysis further showed the capability of rutin to make complex with TNF-α and block its interaction with the target site. CONCLUSION: Aqueous fraction showed maximum hepatoprotective potential as conceived through in vitro and in vivo studies. Presence of rutin may explain hepatoprotective potential of P. divaricata.

A Comprehensive Review on Medicinal Herbs and Novel Formulations for the Prevention of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases reported in the aging population across the globe. About 46.8 million people are reported to have dementia, and AD is mainly responsible for dementia in aged people. Alzheimer's disease (AD) is thought to occur due to the accumulation of ß-amyloid (Aß) in the neocortex portion of the brain, nitric oxide mediated dysfunctioning of blood-brain barrier, reduced activity of serine racemase enzyme, cell cycle disturbances, damage of N-methyl-D-aspartate (NMDA) receptors and glutamatergic neurotransmission. Modern treatment methods target the pathways responsible for the disease. To date, solely symptomatic treatments exist for this disease, all making an attempt to counterbalance the neurotransmitter disturbance. Treatments able to prevent or at least effectively modifying the course of AD, referred to as 'disease-modifying' drugs, are still under extensive research. Effective treatments entail a better indulgence of the herbal bioactives by novel drug delivery systems. The herbal bioactive administered by novel drug delivery systems have proved beneficial in treating this disease. This review provides detailed information about the role of medicinal plants and their formulations in treating Alzheimer's disease which will be highly beneficial for the researchers working in this area.

Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals.

Developmental exposure to endocrine disrupting chemicals (EDCs), e.g., bisphenol A (BPA) or genistein (GEN), causes longstanding epigenome effects. MicroRNAs (miRs) regulate which mRNAs will be translated to proteins and thereby serve as the final checkpoint in epigenetic control. Scant amount is known, however, whether EDCs affect neural miRNA (miR) patterns. We aimed to test the hypothesis that developmental exposure of California mice (Peromyscus californicus) to GEN, BPA, or both chemicals influences hypothalamic miR/small RNA profiles and ascertain the extent such biomolecular alterations correlate with behavioral and metabolic changes. California mice were developmentally exposed to GEN (250 mg/kg feed weight, FW), GEN (250 mg/kg FW)+BPA (5 mg/kg FW), low dose (LD) BPA (5 mg/kg FW), or upper dose (UD) BPA (50 mg/kg FW). Adult offspring were tested in a battery of behavioral and metabolic tests; whereupon, mice were euthanized, brains were collected and frozen, small RNAs were isolated from hypothalamic punches, and subsequently sequenced. California mice exposed to one or both EDCs engaged in one or more repetitive behaviors. GEN, LD BPA, and UD BPA altered aspects of ultrasonic and audible vocalizations. Each EDC exposure led to sex-dependent differences in differentially expressed miR/small RNAs with miR7-2, miR146, and miR148a being increased in all female and male EDC exposed groups. Current findings reveal that developmental exposure to GEN and/or BPA affects hypothalamic miR/small RNA expression patterns, and such changes correlate with EDC-induced behavioral and metabolic alterations. miR146 is likely an important mediator and biomarker of EDC exposure in mammals, including humans.

Protective role of Phyllanthusfraternus in alloxan-induced diabetes in rats.

BACKGROUND: Phyllanthusfraternus is a pantropical weed of family phyllanthaceae, mainly found in northeast India. It has been used in the folklore medicine of Manipur tribe for treating type 2 diabetes. OBJECTIVE: The present study was commenced to evaluate the anti-diabetic and renoprotective potential of P.fraternus (aerial parts) in alloxan-induced diabetes in rats. MATERIALS AND METHODS: Alloxan (130 mg/kg, ip) was used for the induction of diabetes in adult male wistar rats. Animals with blood glucose level greater than 280 mg/dL were treated once daily for 14 days with various test extracts. The biochemical parameters were measured from serum on the 15th day post-treatment. Necropsy samples harvested from pancreas and kidneys were examined for histopathological changes in these organs. RESULTS: Alloxan-induced diabetes not only caused significant increases in blood glucose, triglycerides, total cholesterol, creatinine and urea levels, but also provoked high oxidative stress in pancreas and kidneys. Profound morphological injuries were observed in islets of Langerhans and kidneys of diabetic animals. Administration of methanol extract (200 and 400 mg/kg) and mother liquor (200 and 400 mg/kg) ameliorate the elevated levels of blood glucose, triglycerides, total cholesterol as well as other biochemical parameters, but highest reduction in blood glucose concentration was observed with the largest dose of ethyl acetate fraction (400 mg/kg) of P.fraternus. Histopathological examination of pancreas and kidneys also exhibited greater protection by treatment with acetate fraction (400 mg/kg). The HPLC analysis showed the presence of four polyphenols such as catechin, gallic acid, caffeic acid and ellagic acid in ethyl acetate fraction of P. fraternus during HPLC analysis. CONCLUSION: The results suggest that polyphenols present in P.fraternus may be responsible for the anti-diabetic and renoprotective activity in rats. Such protective effects of could be mediated through flavonol-induced anti-oxidant and anti-inflammatory activities in the pancreas and kidneys.

Anti-inflammatory effect of methanolic extract of Gmelina arborea bark and its fractions against carrageenan induced paw oedema in rats.

Gmelina arborea has been traditionally used for treatment of abdominal pain, burning sensation and as stomachic. The anti-inflammatory effect of aqueous and methanol extract of this plant has been studied but detailed investigations on anti-inflammatory activity of G. arborea stem bark are still not available. Therefore, the present study was designed to evaluate the anti-inflammatory activity of methanol extract and its fractions using carrageenan induced paw oedema model. Methanol extract at the dose of 500 mg/kg and its ethyl acetate fraction at 50 mg/kg showed significant reduction in paw oedema in comparison with standard drug. Ethyl acetate fraction was subjected to column chromatography which resulted in isolation of a new flavonoid (GM-01). Anti-inflammatory effect of methanol extract and its fractions can be attributed to the presence of the flavonoid GM-01. Further studies are underway for evaluation of anti-inflammatory effect of GM-01 and identification of active constituents present in ethyl acetate fraction.

Tacalcitol: a useful adjunct to narrow-band ultraviolet-B phototherapy in vitiligo.

BACKGROUND: Phototherapy especially narrow-band UV-B (NBUVB) has been considered as mainstay of therapy in nonsegmental vitiligo (generalized type). Topical tacalcitol has also been claimed to be effective, either as monotherapy or as combination therapy. PURPOSE: Comparison of clinical efficacy and safety of NBUVB in combination with topical tacalcitol vs. NBUVB alone in vitiligo. MATERIAL & METHODS: Thirty patients with symmetrical vitiliginous lesions were enrolled for 24 weeks. Patients were instructed to apply tacalcitol ointment on right side of body once daily. In addition, the whole body was irradiated with NBUVB thrice weekly. All the patients were examined, and lesional photography was done. Patients were also followed up for 6 months post-treatment. RESULTS: Our study resulted in two key findings: (1) There was a statistically significant difference in mean percentage of repigmentation at 8, 16 and 24 weeks between combination therapy and NBUVB. (2) The mean cumulative dose and number of treatment sessions for initial repigmentation were significantly lower with combination therapy. No serious adverse effects were observed during the study period. CONCLUSION: Topical tacalcitol potentiates efficacy of NBUVB as it enhances extent of pigmentation, decrease time to repigmentation and lowers the cumulative doses of NBUVB, thereby leading to greater patient satisfaction and improved compliance.

Narrowband UVB phototherapy in pityriasis rosea.

OBJECTIVE: Pityriasis rosea (PR) is an acute self-limiting disease. Despite vigorous efforts by generations of researchers since nearly 150 years, present treatment modalities for PR are not very gratifying. Ultraviolet radiation has been recommended in PR, although only a few studies validate this proposal. This study was conducted to explore the therapeutic effect of NBUVB on the symptoms, course, and severity of PR. MATERIALS AND METHODS: This study involved a hundred patients who were randomly divided into two groups, using computer-generated randomization chart. Group A underwent treatment with fixed dose NBUVB of 250 mJ/cm(2) three times (nonconsecutive) a week for 4 weeks. Group B formed the placebo group who did not receive any treatment. The two groups were compared with each other for the intensity of pruritis, course and duration of disease, and PR severity score (PRSS). RESULTS: The t values of improvement in PRSS score in Group A (t = 12.796) were higher as compared with that in Group B (t = 10.066). Similarly, the t value of the pruritus scale in Group A (t = 7.758) was higher than Group B (t = 5.754) indicating the symptomatic improvement in itching. CONCLUSION: Fixed-dose NBUVB phototherapy resulted in marked improvement in the severity and symptoms of the disease as quantitatively assessed by PRSS.

Anxiolytic effects of Equisetum arvense Linn. extracts in mice.

The petroleum ether (PE), chloroform (CH), ethanol (ETH) and water extracts of E. arvense stems were evaluated for anti-anxiety activity in mice using elevated plus maze model. Ketamine induced hypnosis and actophotometer was used to evaluate sedative effect with various extracts in mice. The results were compared with standard drug diazepam. The ethanolic extract of E. arvense (50 and 100 mg/kg) significantly increased the time-spent and the percentage of the open arm entries in the elevated plus-maze model which was comparable to diazepam. Ethanolic extract (100 mg/kg) prolonged the ketamine-induced total sleeping time and decreased the locomotor activity in mice. The results suggest that the ethanolic extract of E. arvense seems to possess anxiolytic effect with lower sedative activity than that of diazepam. The results could be attributed to the flavonoid content of the ethanolic extract.

Antinociceptive activity of chronic administration of different extracts of Terminalia bellerica Roxb. and Terminalia chebula Retz. fruits.

The petroleum ether (PE), chloroform (CH), ethanol (ETH) and water extracts of Terminalia bellerica and T. chebula fruits were evaluated for their analgesic activity using the tail immersion model in mice. The ethanolic extracts of both the plants exhibited analgesic response at 200,400 and 800mg/kg. The studies were further carried for 15 days to evaluate the effect of these extracts in chronic pain and maximum analgesic response was observed on 14th day in both the plants. Phytochemical investigation of ethanolic extract of the fruits of Terminalia bellerica and T. chebula revealed the presence of saponins, triterpenoids, carbohydrates, tannins and proteins. The results indicate that fruits of T. bellerica and T. chebula could be considered as potential candidate for bioactivity-guided isolation of natural analgesic agents used in the management of chronic pain.