Pentacyclic triterpenoids from the stem of Grewia bracteata Roth demonstrate promising inhibition on tumour cells.

Grewia bracteata Roth stem was investigated for its anticancer potential for the first time. Initially, polarity-guided extracts from three solvents were screened on HeLa, HCT- 116 and MCF-7 tumours cells. The results revealed that ethyl acetate extract (GSE) significantly (p < 0.05) inhibited HeLa, HCT- 116 and MCF-7 cells with respective IC50 values of 30.58, 14.26 and 22.91 µg/mL. GSE inhibited HCT-116 cells with 6- and 21-folds higher than hexane (GSN) and methanol (GSM) extracts, respectively. Hence, column chromatography of GSE was performed and fractionated to 18 fractions. The obtained fractions were further tested on HCT-116 cells. Amongst, the fractions HF6 and DF1 were active with the respective IC50 values of 25.35 and 31.28, µg/mL (p < 0.05). These active fractions were profiled using H1-NMR, C13-NMR and LC-MS/MS analysis, and found the presence of pentacyclic triterpenoids like betulin diacetate and ursolic acid.

Tracking the Variations in Trace Elements, Some Nutrients, Phenolics, and Anthocyanins in Grewia asiatica L. (Phalsa) at Different Fruit Development Stages.

Grewia asiatica L. (phalsa) is a very prevalent berry in Pakistan and is consumed extensively as raw or in the form of juice. Here, for the first time, we assessed phalsa from Pakistan in terms of variations in macro and micro minerals, nutrients, and bio-active phyto-constituents including total phenolic and anthocyanin contents at different fruit developmental stages. It was found that the sugars in phalsa increased from D1 (small at the initial fruit setting stage) to D6 development stage (fully ripened fruit) where sugars at D5 (near to fully ripe) and D6 stages were many times greater than at D1, D2 (unripe close to full-size completion), D3 (close to semi ripe), and D4 stage (semi ripened and full-size attainment). Total acidity of was declined in all developmental stages, where the D1 stage displayed maximum and D6 with the lowest acidity. Ascorbic acid was decreased from D1 to D2 and then increased gradually from D3 to D5 stages. At the D6 stage, again a steep decline in ascorbic acid was observed. The total phenolics (mg gallic acid equivalents/100g) at stage D6 were higher (136.02 ± 1.17), whereas D1 being the lowermost in total phenolic content (79.89 ± 1.72). For anthocyanins (mg/100g), an increasing pattern of changes was observed in all stages of phalsa fruit where the D1 stage showed lower (13.97 ± 4.84) anthocyanin contents which then increased gradually at stage D2 (67.79 ± 6.73), but increased sharply at D3 (199.66 ± 4.90), D4 (211.02 ± 18.85), D5 (328.41 ±14.96) and D6 (532.30 ± 8.51) stages. A total of four anthocyanins such as cyanidin, delphidine-3-glucoside, pelargonidin, and malvidin in phalsa were identified using HPLC procedures, and a significant > 90 % DPPH inhibition in phalsa was observed at the D5 and D6 development stages. The macro and micro minerals including Ni, Zn, Fe, Ca, Cu, Mg, Na, P, and K contents were decreased from initial (D1) stage to the final (D6) development stage, while only Fe displayed an increasing trend from the initial to final fruit development stages (D1-D6). Conclusively, these findings could be of great interest for patients who are intended to consume phalsa as adjuvant therapy against diabetes and metabolic syndromes and other diseases involving reactive oxygen species with minimum metal toxicity.

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.

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.

The Chemical Composition and Health-Promoting Effects of the Grewia Species-A Systematic Review and Meta-Analysis.

Globally grown and organoleptically appreciated Grewia species are known as sources of bioactive compounds that avert the risk of communicable and non-communicable diseases. Therefore, in recent years, the genus Grewia has attracted increasing scientific attention. This is the first systematic review which focusses primarily on the nutritional composition, phytochemical profile, pharmacological properties, and disease preventative role of Grewia species. The literature published from 1975 to 2021 was searched to retrieve relevant articles from databases such as Google Scholar, Scopus, PubMed, and Web of Science. Two independent reviewers carried out the screening, selection of articles, and data extraction. Of 815 references, 56 met our inclusion criteria. G. asiatica and G. optiva were the most frequently studied species. We found 167 chemical compounds from 12 Grewia species, allocated to 21 categories. Flavonoids represented 41.31% of the reported bioactive compounds, followed by protein and amino acids (10.7%), fats and fatty acids (9.58%), ash and minerals (6.58%), and non-flavonoid polyphenols (5.96%). Crude extracts, enriched with bioactive compounds, and isolated compounds from the Grewia species show antioxidant, anticancer, anti-inflammatory, antidiabetic, hepatoprotective/radioprotective, immunomodulatory, and sedative hypnotic potential. Moreover, antimicrobial properties, improvement in learning and memory deficits, and effectiveness against neurodegenerative ailments are also described within the reviewed article. Nowadays, the side effects of some synthetic drugs and therapies, and bottlenecks in the drug development pathway have directed the attention of researchers and pharmaceutical industries towards the development of new products that are safe, cost-effective, and readily available. However, the application of the Grewia species in pharmaceutical industries is still limited.

Pharmacological basis for the antihypertensive activity of Grewia asiatica fruit extract.

In the management of cardiovascular disorders, medicines from herbal sources have played a vital role through centuries. The following study was commenced in order to lay possible pharmacological foundation associated with medicinal uses of edible fruit of Grewia asiatica in hypertension through in-vitro method. In this study isolated atrial preparation of Guinea pig was used where crude ethanolic extract of Grewia asiatica fruit (Ga.Cr) decreased the force and rate of spontaneous atrial contractions (0.03-10mg/kg). In isolated rat aortic ring preparations previously vasoconstricted by phenylephrine and High K+, it also resulted in dose dependent vasodilation (0.01-10 mg/kg).In the presence of L-NAME, the relaxation curve of Ga.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. The speculative analysis contemplated that Ga.Cr has blood pressure reducing potentials through inhibition of Ca++ influx via Ca++ channels, its release from intracellular stores and through other means like NO mediated pathways.

Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret.

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2'-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC50 of 55 µg/mL (against AChE) and 60 µg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50 values of 60 and 62 µg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC50 values for inhibition of the two enzymes were recorded as 90 and 92 µg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer's disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.

Physicochemical Characterization of Grewia ferruginea Hochst. ex A. Rich Mucilage for Potential Use as a Pharmaceutical Excipient.

Gum and mucilages from natural sources are in recent times increasingly investigated for pharmaceutical applications. Different studies have shown that the gum and mucilage fraction of various species of the genus Grewia were found to be effective viscosity enhancers, stabilizers, disintegrants, suspending agents, gelling agents, bioadhesives, film coating agents, and binders. However, no study has been conducted on the potential use of Grewia ferruginea mucilage (GFM) as a pharmaceutical excipient. Therefore, this study was aimed at characterizing the Grewia ferruginea bark mucilage for its potential use as a pharmaceutical excipient. The mucilage was extracted from the Grewia ferruginea inner stem bark through aqueous extraction, precipitated with 96% ethanol, dried, and powdered. The powdered mucilage was characterized for different physicochemical properties such as powder property, loss on drying, solubility and swelling index, ash value, pH, viscosity, moisture sorption property, microbial load, and acute oral toxicity. According to the results, the percentage yield of the final dried and powdered GFM was found to be 11.96% (w/w). The density and density-related properties of the mucilage showed good powder flow property. The GFM exhibited pseudoplastic flow behavior. Moisture sorption property of GFM revealed its hygroscopic nature, and its solubility and swelling property was increased with temperature. The pH of GFM was near neutral. Microbial load of the mucilage was within the pharmacopoeial limit, and the oral acute toxicity test revealed that the mucilage is safe up to 2000 mg/kg. From the investigations of this study, it can be concluded that Grewia ferruginea bark mucilage has the potential to be utilized as an excipient in pharmaceutical formulations.

Mechanical and release behaviour of theophylline from matrix tablets containing psyllium powder in combination with grewia polysaccharides.

This study was aimed at investigating the effect of grewia polysaccharides on the mechanical and release properties of tablet matrices containing binary mixtures of the polysaccharide with psyllium. Two grades of grewia polysaccharides (GG and GDS) were extracted and binary mixtures of the polysaccharides with psyllium were formulated into tablet matrices containing theophylline as the model drug. The true, bulk and tapped densities, Carr's compressibility index of the powders and binary composites were determined before tablet compression. Tablet properties (hardness, porosity, and drug release from the matrices) were investigated. The dissolution test was carried out in 0.1 M HCl (pH 1.2) and phosphate buffer (pH 6.8). The results show that GG and GDS produced tablets with good mechanical strength (108.33 N and 95.70 N, respectively) while psyllium produced softer tablets (7.13 N). The combination of psyllium and grewia polysaccharides in the matrices resulted in a significant increase in the mechanical strength of the matrices when compared to matrices containing psyllium alone as the matrix former. The results also showed that GG and GDS reduced the dissolution rate and effectively eliminated the burst release of theophylline from the psyllium matrices at both pHs. The matrices of GG or GDS and the binary mixtures conform to non-Fickian anomalous diffusion with n > 0.45. When overcoming the burst release of drug from matrices such as psyllium, grewia polysaccharides may provide an effective reduction and a more sustained drug release from such matrices.

Toxicological, anticholinesterase, antilipidemic, antidiabetic and antioxidant potentials of Grewia optiva Drummond ex Burret extracts.

Background In this study, Grewia optiva Drummond ex Burret root extracts were assessed for use as a remedy for oxidative stress, diabetes mellitus and neurological disorders. Methods The antioxidative potentials of the extracts were determined using DPPH and ABTS assays, whereas their enzyme inhibitory potentials were determined against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase and α-amylase. In the in vivo experiments, methanol extract was orally administered to mice (n = 5) at four doses of 200, 300, 400 and 500 mg kg-1 for 30 days and its effect on glucose, triglycerides, total cholesterol, etc. were investigated. Results The highest free radical scavenging activities against DPPH and ABTS radicals were recorded for the methanol and ethyl acetate extracts, and their respective IC50 values were 75 and 88 µg/mL. In addition, these two fractions were highly active in inhibiting AChE and BChE, with IC50 values of 120 and 185 µg/mL, respectively. Moderate inhibition (µg/mL) was recorded against α-glucosidase (69.02 ± 1.02 and 64.29 ± 2.41) and α-amylase (65.12 ± 2.02 and 63.29 ± 1.41) and these were comparable to the inhibitory activities exhibited by the standard, acarbose. All the extracts showed high phenolic and flavonoid contents, which correlated with their antioxidant, anticholinesterase, α-glucosidase and α-amylase activities. The phenolic compounds in the crude extract and fractions were determined using the standard HPLC method and bioactive compounds, namely, morin, ellagic acid, kaempferol-3-(p-coumaroyl-diglucoside)-7-glucoside, apigenin-7-O-rutinoside, quercetin-3-(caffeoyl-diglucoside)-7-glucoside, etc., which were detected at various retention times. Significant decrease in cholesterol, triglyceride and blood glucose levels were observed. Conclusion G. optiva is a good source of antioxidants and other phytochemicals, some of which possess anticholinesterase, anti-glucosidase, and anti-amylase activities, and can be used to treat different health conditions such as oxidative stress, neurological disorders, and diabetes mellitus.

Isolation, pharmacological evaluation and molecular docking studies of bioactive compounds from Grewia optiva.

BACKGROUND: Traditionally, Grewia optiva is widely used for the treatment of many diseases like dysentery, fever, typhoid, diarrhea, eczema, smallpox, malaria and cough. METHODS: Shade-dried roots of G. optiva were extracted with methanol. Based on HPLC results, chloroform and ethyl acetate fractions were subjected to silica column isolation and four compounds: glutaric acid (V), 3,5 dihydroxy phenyl acrylic acid (VI), (2,5 dihydroxy phenyl) 3',6',8'-trihydroxyl-4H chromen-4'-one (VII) and hexanedioic acid (VIII) were isolated in pure form. Ellman's assay was used to determine the anticholinesterase potential of isolated compounds while their antioxidant potential was estimated by DPPH and ABTS scavenging assays. RESULTS: Amongst the isolated compounds, VI and VII exhibited excellent percent inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (83.23±1.11, 82.72±2.20 and 82.11±2.11, 82.23±1.21, respectively, at 1000 µg/mL) with IC50 of 76, 90, 78 and 92 µg/mL, respectively. Highest percent radicals scavenging against DPPH and ABTS (87.41±1.20 and 86.13±2.31) with IC50 of 64 and 65 µg/mL, respectively, were observed for compound VII. Molecular docking studies also supported the binding of compound VI and VII with the target enzyme. The para-hydroxyl group of the phenolic moiety is formed hydrogen bonds with the active site water molecule and the side chain carbonyl and hydroxyl residues of enzyme. CONCLUSION: The isolated compounds inhibited the DPPH and ABTS-free radicals, and AChE and BChE enzymes. It was concluded that these compounds could be used in relieving the oxidative stress and pathological symptoms associated with excessive hydrolysis of acetyl and butyryl choline. The results of the study were supported by docking studies for compounds VI and VII.

Biogenic synthesis of iron oxide nanoparticles using Agrewia optiva and Prunus persica phyto species: Characterization, antibacterial and antioxidant activity.

A phytoextract mediated synthesis of iron oxide nanoparticles using Agrewia optiva (Dhaman or Biul) and Prunus persica (Peach) leaf extract as capping and stabilizing agent without using hazardous toxic chemicals via biogenic route has been studied. The biogenic method of synthesis is convenient, rapid, cost effective and ecofriendly. The green synthesized nanoparticles were characterized by Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, Attenuated total reflectance spectroscopy, X-ray diffraction analysis, scanning electron microscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy and dynamic light scattering measurements. The antibacterial study was determined by agar well diffusion method to measure the efficiency of both phyto species extract and its mediated iron oxide nanoparticles against five gram positive bacterial stains such as Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), Streptococcus pyrogenes (S. pyrogenes), Corynebacterium diphtheriae (C. diphtheriae) and Corynebacterium xerosis (C. xerosis) and three gram negative bacterial stains such as Escherichia coli (E. coli), Klebsiella pneuomoniae (K. pneuomoniae) and Pseudomonas aeruginosa (P. aeruginosa). The antibiotic Ciprofloxacin and Gentamicin have been used as reference standard drugs for gram positive and gram negative bacterial stains, respectively. The antioxidant activity of the phyto extracts and prepared nanoparticles have been performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay employing l-ascorbic acid as a standard.

Grewia tiliaefolia and its active compound vitexin regulate the expression of glutamate transporters and protect Neuro-2a cells from glutamate toxicity.

AIM: Glutamate is a major neurotransmitter involved in several brain functions and glutamate excitotoxicity is involved in Alzheimer's disease (AD). In the current study, the neuroprotective effect of the Indian medicinal plant Grewia tiliaefolia (GT) and its active component vitexin was evaluated in Neuro-2a cells against glutamate toxicity. MATERIALS AND METHODS: Neuro-2a cells were exposed to glutamate to cause excitotoxicity and the neuroprotective effect of GT and vitexin were evaluated using biochemical studies (estimation of reactive oxygen species, reactive nitrogen species, protein carbonyl content, lipid peroxidation level, mitochondrial membrane potential and caspase-3 activity), molecular docking studies, gene expression and western blot analysis. KEY FINDINGS: Glutamate exposure to Neuro-2a cells induced oxidative stress, loss of membrane potential, suppressed the expression of antioxidant response genes (Nrf-2, HO-1, NQO-1), glutamate transporters (GLAST-1, GLT-1) and induced the expression of NMDAR, Calpain. However, pre-treatment of cells with GT/vitexin inhibited oxidative stress mediated damage by augmenting the expression of Nrf-2/HO-1 pathway, inducing the expression of glutamate transporters and downregulating Calpain, NMDAR. Molecular docking showed that vitexin effectively binds to NMDAR and GSK-3ß and thereby can inhibit their activation. GT/vitexin also inhibited glutamate induced Bax expression. SIGNIFICANCE: Methanol extract of G. tiliaefolia and its active component vitexin can act in an antioxidant dependent mechanism as well as by regulating glutamate transporters in mitigating the toxicity exerted by glutamate in Neuro-2a cells. Our results conclude that GT/vitexin can act as potential drug leads for the therapeutic intervention of AD.

Anti-bacterial, free radical scavenging activity and cytotoxicity of acetone extracts of Grewia flava.

BACKGROUND: Bacterial infections of the gastrointestinal tract (GIT) cause vomiting, diarrhoea and even systemic disease. There is a need for the development of natural products into alternative and safer medicines. OBJECTIVES: This study evaluated the anti-microbial activity of extracts prepared from berries, leaves, bark and roots of the edible plant Grewia flava. METHODS: The anti-bacterial activity was evaluated by the broth microdilution method. Anti-oxidant activity of the most active extracts was performed by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The cytotoxicity of the extracts was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The acetone extracts of the leaves and roots showed the best activity with MIC values as low as 0.03 mg/mL against Staphylococcus aureus and Salmonella typhimurium and 0.07 mg/mL against Bacillus cereus, Escherichia coli and Staphylococcus aureus. Quantitative analysis of the scavenging ability showed that acetone extracts exhibited good free radical scavenging activity in a dose-dependent manner. The berries extract had the highest LC50 (lowest toxicity) of 551.68 68 µg/mL. CONCLUSION: Acetone extract of leaves and roots of Grewia flava contain anti-microbial and anti-oxidant compounds and could therefore be used as a natural product with little toxicity to host cells.

Quick Identification of Piperidine Alkaloid from Roots of Grewia nervosa and Their Glucosidase Inhibitory Activity.

Grewia nervosa is a herbal plant used in traditional medicine for different purposes. Bioassay-guided chemical fractionation of G. nervosa roots resulted in an identification of two known and one new compound, namely microgrewiapine A, homomicrogrewiapine, and N-methylmicrocosamine, respectively. Their structures were determined using combination of LC/HR-MS, 1 H-NMR, and IR spectral analyses and followed by comparison with those reported in the literature. The problematic separation of these alkaloids on traditional column chromatography (Silica gel, Octadecyl silane, Sephadex) was resolved by using HPLC. Structurally similar compounds from the piperidine family have been characterized by using HR-MS analysis in combination with NMR data of crude samples. The major constituent i.e. N-methylmicrocosamine isolated from the butanol fraction of methanol root extract (MRE) was found to possess the dose dependent α-glucosidase inhibition activity with an IC50 value of 53.40 µm. Furthermore, N-methylmicrocosamine showed maximum α-glucosidase inhibition of 97.48 ± 0.7% at 107.5 µm, which is approximately 1.3 × 103 fold higher than the activity shown by acarbose (97.72% inhibition at 61.95 mm), a standard anti-diabetic drug available commercially. This work also reports the in vitro α-glucosidase inhibitory activity of the major alkaloids isolated from G. nervosa for the first time.

Beta sitosterol and Daucosterol (phytosterols identified in Grewia tiliaefolia) perturbs cell cycle and induces apoptotic cell death in A549 cells.

Lung cancer is the leading cause of cancer related deaths both in developed and developing countries. Since majority of the existing therapeutic methods harms both normal and malignant cells, a viable alternative is to switch into safe and beneficial traditional medicinal plants. Hence the present study was framed to identify selective anti-lung cancer agents from the medicinal plant Grewia tiliaefolia (GT). Cell viability experiments showed that benzene extract of GT (BGT) leaf effectively inhibited the growth of A549 cells, while being non-toxic to normal human lung L132 and PBMC cells. Ames and comet assays demonstrated that BGT is of non-mutagenic and non-genotoxic nature in untransformed cells. The hematological and histopathological profiles of the in vivo acute and sub-acute toxicity studies demonstrated that BGT is safe and tolerable. Importantly, western blot analysis and Annexin V-FITC staining confirmed that BGT promotes mitochondrial dependent apoptotic cell death in A549 cells by arresting cell cycle at G2/M phase. Bio-assay guided fractionation revealed the presence of phytosteols (ß-sitosterol and daucosterol) which significantly inhibited the growth of A549 cells both alone and in combination. This study warrants that these phytosterols in alone or in combination can be considered as safe and potential drug candidates for lung cancer treatment.

Cholinesterase inhibitory, anti-amyloidogenic and neuroprotective effect of the medicinal plant Grewia tiliaefolia - An in vitro and in silico study.

CONTEXT: Grewia tiliaefolia Vahl. (Tiliaceae) is a sub-tropical plant used as an indigenous medicine in India. However, its efficacy has not been evaluated against Alzheimer's disease. OBJECTIVES: The objective of this study is to evaluate cholinesterase inhibitory, anti-aggregation and neuroprotective activity of G. tiliaefolia. MATERIALS AND METHOD: Grewia tiliaefolia leaves were collected from Eastern Ghats region, India, and subjected to successive extraction (petroleum ether, chloroform, ethyl acetate, methanol and water). The extracts were subjected to in vitro antioxidant, anticholinesterase and anti-aggregation assays. The active methanol extract (MEGT) was separated using column chromatography. LC-MS analysis was done and the obtained compounds were docked against acetylcholinesterase (AChE) enzyme to identify the active component. RESULTS: Antioxidant assays demonstrated that the MEGT showed significant free radical scavenging activity at the IC50 value of 71.5 ± 1.12 µg/mL. MEGT also exhibited significant dual cholinesterase inhibition with IC50 value of 64.26 ± 2.56 and 54 ± 0.7 µg/mL for acetyl and butyrylcholinesterase (BChE), respectively. Also, MEGT showed significant anti-aggregation activity by preventing the oligomerization of Aß25-35. Further, MEGT increased the viability of Neuro2a cells up to 95% against Aß25-35 neurotoxicity. LC-MS analysis revealed the presence of 16 compounds including vitexin, ellagic acid, isovitexin, etc. In silico analysis revealed that vitexin binds effectively with AChE through strong hydrogen bonding. These results were further confirmed by evaluating the activity of vitexin in vitro, which showed dual cholinesterase inhibition with IC50 value of 15.21 ± 0.41 and 19.75 ± 0.16 µM for acetyl and butyrlcholinesterase, respectively. DISCUSSION AND CONCLUSION: Grewia tiliaefolia can be considered as a promising therapeutic agent for the treatment of AD.

Antidiabetic, antihyperlipidemic and antioxidant properties of ethanol extract of Grewia asiatica Linn. bark in alloxan-induced diabetic rats.

BACKGROUND: Inspite of introduction of oral hypoglycemic agents, diabetes and its related complications remains to be a major clinical problem. The aim of this study was to investigate the antidiabetic, antihyperlipidemic and antioxidant activities of Grewia asiatica (Linn) stem bark in alloxan induced diabetic rats. METHODS: Diabetes was induced by a single dose of intraperitoneal injection of alloxan (110 mg/kg) in Norwegian Long Evans rats. Ethanol extract of barks from Grewia asiatica (GAE 200 and 400 mg/kg) and metformin (150 mg/kg) were orally administered once daily for 15 days. Blood glucose levels and body weights of rats were measured on 0, 5, 10 and 15 days of oral treatment. At the end of the experiment the rats were sacrificed and blood sample were collected for the measurement of total cholesterol (TC), triglycerides (TG), very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), SGOT and CK-MB. Analysis of liver glycogen content and histopathlogy of pancreas were carried out. In vitro DPPH free radical scavenging activity, total phenolic and total flavonoid content of GAE were also determined. RESULTS: After 15 days of oral administration of GAE at doses of 200 and 400 mg/kg increased survival rate and showed a significant attenuation in blood glucose and lipid profile in diabetic rats. Oral ingestion of GAE significantly reduced the SGOT and CK-MB levels and restored liver glycogen content when compared to diabetic control. The effects of GAE on SGOT, CK-MB and liver glycogen content were dose-dependent. The diabetic rats treated with GAE showed significant improvement in normal cellular population size of islets. Phytochemical screening of GAE revealed the presence of flavonoid, steroid, tannin and phenolic compounds. Total phenolic content was 44.65 ± 3.17 mg of gallic acid equivalent per gm of GAE extract and the total flavonoid content was 39.11 ± 4.65 mg of quercetin equivalent per gm of GAE extract. In DPPH scavenging assay, IC50 values of GAE and ascorbic acid were found 76.45 and 12.50 µg/ml, respectively. CONCLUSION: We demonstrated that ethanol extract of barks from G. asiatica possess glucose, lipid lowering efficacy, restored liver glycogen and protects pancreas from oxidative damage in alloxan-induced diabetic rats. Thus, the results of the present study provide a scientific rationale for the use of G. asiatica in the management of diabetes and its related complications.

Antioxidant, Antimicrobial Activity and Medicinal Properties of Grewia asiatica L.

Since ancient time, India is a well known subcontinent for medicinal plants where diversity of plants is known for the treatment of many human disorders. Grewia asiatica is a dicot shrub belonging to the Grewioideae family and well known for its medicinally important fruit commonly called Falsa. G. asiatica, a seasonal summer plant is distributed in the forest of central India, south India, also available in northern plains and western Himalaya up to the height of 3000 ft. Fruits of G. asiatica are traditionally used as a cooling agent, refreshing drink, anti-inflammatory agent and for the treatment of some urological disorders. Recent advancement of Falsa researches concluded its antimicrobial and anti-diabetic activity. Since ancient time medicinal plants are traditionally used for the treatment of different diseases G. asiatica fruit is the edible and tasty part of the plant, now considered as a valuable source of unique natural product for the development of medicines which are used in different disease conditions like anti-diabetic, anti-inflammatory, anti-cancerous and antimicrobial. Now a days, G. asiatica is being used in different Ayurvedic formulation for the cure of different types of diseases. Different pharmacological investigations reveal the presence of phenols, saponnins, flavonoids and tannins compound in the fruits. Present review highlights the phytopharmacological and different traditional use of G. asiatica which is mentioned in ancient Ayurvedic texts. This review stimulates the researchers and scientists for further research on G. asiatica.

Antihyperglycemic Potential of Grewia asiatica Fruit Extract against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms.

Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications. In folk medicine, the edible Grewia asiatica fruit is used in a number of pathological conditions. This study aimed to investigate the possible curative effect of G. asiatica fruit ethanolic extract against streptozotocin- (STZ-) induced hyperglycemia in rats. Furthermore, mechanism of antihyperglycemic action is investigated. Hyperglycemic rats are either treated with 100 or 200 mg/kg/day G. asiatica fruits extract. Serum glucose, liver glycogen, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin- (IL-) 1ß, and tumor necrosis factor- (TNF-) α are measured. G. asiatica fruits extract reduces blood glucose and pancreatic MDA levels. It increases liver glycogen and pancreatic GSH contents and SOD enzyme activity. Furthermore, Grewia asiatica fruits extract decreases serum IL-1ß and TNF-α. The treatment also protects against STZ-induced pathological changes in the pancreas. The results of this study indicated that G. asiatica fruit extract exerts antihyperglycemic activity against STZ-induced hyperglycemia. The improvement in the pancreatic ß-cells and antioxidant and anti-inflammatory effects of G. asiatica fruit extract may explain the antihyperglycemic effect.