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.

Anticancer effect of polyphenolic acid enriched fractions from Grewia bracteata Roth on tumor cells and their p53 gene independent ROS mediated apoptosis in colon cancer cells.

It is the first report on leaves of Grewia bracteata Roth for its anticancer effect. In this study, three polarity-guided solvent extracts of Grewia bracteata leaves from n-hexane (GLH), ethyl acetate (GLE), and methanol (GLM) were screened for anticancer effects on HeLa, HCT-116, MCF-7, HCT-116 p53-/- and PC-3 cells via methyl thiazoldiphenyltetrazolium bromide (MTT) assay. Based on the results, GLM was fractionated, and the obtained fractions were tested on HCT-116 cells. Further, FT-IR, HPLC analysis, clonogenic assay, wound healing assay, DCFDA, and cell cycle experiments were conducted on HCT-116 cells. The extracts from methanol (GLM) and ethyl-acetate (GLE) demonstrated a more selective and promising inhibition on HCT-116 cells than others. Notably, GLM recorded superior inhibition on HCT-116 p53-/- than GLE. Amongst, the methanol column fraction (GMCF) showed prominent inhibition on HCT-116 (IC50:63.55 ± 0.61 µg/ml) and HCT-116 p53-/- (IC50: 84.51 ± 0.58 µg/ml) cells. Further, the test on normal cells (NKE) revealed minimal toxicity of GMCF. The phytochemical test, FT-IR, HPLC, and LC-HRMS analyses confirmed the high abundance of polyphenolic acid/polyphenols in GMCF. Further, the clonogenic and wound healing assays on HCT-116 cells were also performed. Later, the probable cell death mechanism was identified using DCFDA and cell cycle experiments. These experiments disclosed that GMCF induced HCT-116 cell death was probably due to reactive oxygen species (ROS) upregulation and cells cycle arrest at SubG0 phase. It inferred that the activity is most probably p53 independent, a tumor suppressor gene responsible for drug resistance in colon cancer.

Insights into diversity and L-asparaginase activity of fungal endophytes associated with medicinal plant Grewia hirsuta.

L-asparaginase is used as one of the prime chemotherapeutic agents to treat acute lymphoblastic leukemia. The present work aimed to study the endophytic fungal diversity of Grewia hirsuta and their ability to produce L-asparaginase. A total of 1575 culturable fungal endophytes belonging to four classes, Agaricomycetes, Dothideomycetes, Eurotiomycetes, and Sordariomycetes, were isolated. The isolates were grouped into twenty-one morphotypes based on their morphological characteristics. Representative species from each group were identified based on their microscopic characteristics and evaluation of the ITS and LSU rDNA sequences. Most of the fungal endophytes were recovered from the leaves compared to other plant parts. Diaporthe sp. was the predominant genus with a colonization frequency of 8.62%. Shannon-Wiener index for diversity ranged from 2.74 to 2.88. All the plant parts showed similar Simpson's index values, indicating a uniform species diversity. Among the sixty-three fungal endophytes screened, thirty-two were identified as L-asparaginase-producing isolates. The enzyme activities of fungal endophytes estimated by the nesslerization method were found to be in the range of 4.65-0.27 IU/mL with Fusarium foetens showing maximum enzyme activity of 4.65 IU/mL. This study for the first time advocates the production of L-asparaginase from Fusarium foetens along with the endophytic fungal community composition of Grewia hirsuta. The results indicate that the fungal endophyte Fusarium foetens isolated in the present study could be a potent source of L-asparaginase.

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.

Quantitative Phytochemical Profile and In Vitro Antioxidant Properties of Ethyl Acetate Extracts of Xerophyta spekei (Baker) and Grewia tembensis (Fresen).

Overproduction of free radicals in excess of antioxidants leads to oxidative stress which can cause harm to the body. Conventional antioxidants have drawbacks and are believed to be carcinogenic. The present study seeked to confirm folklore use and validate the antioxidant potentials of Grewia tembensis and Xerophyta spekei which have been widely used in the Mbeere community as medicinal plants. Antioxidant properties were determined through scavenging effects of diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide radicals as well as iron chelating effects. The data obtained was assayed in comparison to the standards (Ascorbic acid and EDTA). Ascorbic acid had a significantly greater DPPH radical scavenging property with an inhibitory concentration (IC50) value of 20.54 ± 2.24 µg/mL in comparison to the plant extracts, which had IC50 values of 33.00 ± 1.47 µg/mL, 69.66 ± 1.01 µg/mL and 86.88 ± 2.64 µg/mL for X. spekei, G. tembensis leaf and G. tembensis stem bark extracts, respectively. EDTA demonstrated a significantly greater iron chelating effect having a significantly lesser IC50 value of 25.05 ± 0.79 µg/mL as opposed to 43.56 ± 0.46 µg/mL, 89.78 ± 0.55 µg/mL, and 120.70 ± 0.71 µg/mL for X. spekei, G. tembensis leaf, and G. tembensis stem bark extracts respectively. Additionally, ascorbic acid also exhibited stronger hydrogen peroxide radical scavenging effect than the studied extracts. Generally, X. spekei extract had higher antioxidant activities as compared to both the leaf and stem bark extracts of G. tembensis. The phytochemical screening demonstrated the presence of secondary metabolites associated with antioxidant properties. The present study therefore, recommends ethno medicinal and therapeutic use of G. tembensis and X. spekei in the treatment and management of oxidative stress related infections.

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 Detailed Pharmacodynamics of the Gut Relaxant Effect and GC-MS Analysis of the Grewia tenax Fruit Extract: In Vivo and Ex Vivo Approach.

The study was performed to assess and rationalize the traditional utilization of the fruit part of Grewia tenax (G. tenax). The phytoconstituents present in the methanolic extract were analyzed using Gas-Chromatography-Mass Spectroscopy (GC-MS), while the anti-diarrheal activity was investigated in the Swiss albino mice against castor oil-provoked diarrhea in vivo. The antispasmodic effect and the possible pharmacodynamics of the observed antispasmodic effect were determined in an isolated rat ileum using the organ bath setup as an ex vivo model. GC-MS findings indicate that G. tenax is rich in alcohol (6,6-dideutero-nonen-1-ol-3) as the main constituent (20.98%), while 3-Deoxy-d-mannoic lactone (15.36%) was detected as the second major constituents whereas methyl furfural, pyranone, carboxylic acid, vitamin E, fatty acid ester, hydrocarbon, steroids, sesquiterpenes, phytosterols, and ketones were verified as added constituents in the methanolic extract. In mice, the orally administered G. tenax inhibited the diarrheal episodes significantly (p < 0.05) at 200 mg/kg (40% protection), and this protection was escalated to 80% with the next higher dose of 400 mg/kg. Loperamide (10 mg/kg), a positive control drug, imparted 100% protection, whereas no protection was shown by saline. In isolated rat ileum, G. tenax completely inhibited the carbamylcholine (CCh; 1 µM) and KCl (high K+; 80 mM)-evoked spasms in a concentrations-mediated manner (0.03 to 3 mg/mL) by expressing equal potencies (p > 0.05) against both types of evoked spasms, similar to papaverine, having dual inhibitory actions at phosphodiesterase enzyme (PDE) and Ca2+ channels (CCB). Similar to papaverine, the inhibitory effect of G. tenax on PDE was further confirmed indirectly when G. tenax (0.1 and 0.3 mg/mL) preincubated ileal tissues shifted the isoprenaline-relaxation curve towards the left. Whereas, pre-incubating the tissue with 0.3 and 1 mg/mL of G. tenax established the CCB-like effect by non-specific inhibition of CaCl2−mediated concentration-response curves towards the right with suppression of the maximum peaks, similar to verapamil, a standard CCB. Thus, the present investigation revealed the phytochemical constituents and explored the detailed pharmacodynamic basis for the curative use of G. tenax in diarrhea and hyperactive gut motility disorders.

Antiinflammatory and Anticancer Properties of Grewia asiatica Crude Extracts and Fractions: A Bioassay-Guided Approach.

The study was an extension of our earlier work on antiinflammatory and anticancer properties of G. asiatica fruit. We aimed to develop a bioassay guided multistep purification technique for producing bioactive fractions of G. asiatica crude extracts. Dried fruit powder was sequentially fractionated with 100% dichloromethane, 100% methanol (MeOH), and 50% MeOH. Active extracts were subjected to liquid-liquid partitioning followed by subfractionation using RP-HPLC. Antioxidant, antiinflammatory, and anticancer activities of the fruit extracts, and their potent fractions were evaluated in vitro, while identification of compounds from the bioactive fractions was performed by ESI-MS/MS analysis. The amount of the identified compounds present was confirmed using external standards adopting a simple, accurate, and rapid analytical HPLC method. The results showed that 100% and 50% MeOH extracts possessed bioactivity; one of which (the 50% MeOH extract) displayed potent activity in all in vitro bioassays. MeOH extract (50%) derived fraction C and hydroalcoholic fraction 5 (GAHAF5) were observed to possess higher antioxidant, antiinflammatory, and in vitro anticancer activity. IC50 of GAHAF5 against MCF-7, HEp-2, and NCI-H522 cancer cells was recorded as 26.2, 51.4, and 63 µg/mL, respectively. ESI-MS/MS and HPLC analysis identified catechin, chlorogenic acid, caffeic acid, and morin as potential bioactive compounds in the GAHAF5 fraction with concentrations of 1230, 491, 957, and 130 µg/g, respectively. The findings indicated that G. asiatica bioactive fractions possessed antiinflammatory activity in vitro and were cytotoxic against breast cancer, lung cancer, and laryngeal cancer cell lines.

Evaluation of cardio protective, anti-inflammatory, analgesic and CNS depressant activity of Grewia asiatica L. fruit extract.

Grewia asiatica L. is a potential medicinal plant used for various diseases in traditional medicine. Current study was aimed to evaluate the cardio protective, anti-inflammatory, analgesic and CNS depressant activities of Grewia asiatica L. fruit extract. In cardio protective activity myocardial injury was produced by injection of Isoproterenol (200 mg/kg, s.c), G. asiatica 250 and 500mg/kg treated groups significantly (p<0.05) decreased the level of serum AST, ALT, LDH and CKMB, hence produced cardio protective effect. In analgesic activities G. asiatica produced significant (p<0.05) analgesic effects in acetic acid induced writhing, formalin, paw pressure and tail immersion test. G. asiatica at 250 and 500mg/kg oral dose, significantly (p<0.05) reduced the rat paw edema in carrageen an induced rat paw edema test. G. asiatica extract also produced significant CNS depressant effects in open field, hole board and thiopental sodium induced sleeping time. Findings of the current study suggest that G. asiatica fruit extract showed potential pharmacological effects and can be utilized in alternative medicine.

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.

The essential oils of Grewia Lasiocarpa E. Mey. Ex Harv.: chemical composition, in vitro biological activity and cytotoxic effect on Hela cells.

The chemical composition and biological activity of the essential oil extracted from the fresh leaves and stem bark of Grewia lasiocarpa was determined for the first time in this study. The essential oils were extracted by hydrodistillation and identified by GC-MS and FTIR. The antibacterial, antioxidant activity and total phenolic content of essential oils were determined. The major compounds identified were phytol (22.6%); α-farnesene (8.62%); n-hexadecanoic acid (7.24%); farnesol (4.61%) in the leaves, and 2-methylheptadecane (7.24%); heptacosane (7.60%); heptadecane, 2,6,10,14-tetramethyl (7.30%). The presence of aromatic, alkanes and phenolic compounds were revealed by FTIR analysis. The in silico oral prediction shows that some of the components are orally safe. The essential oil from the leaves showed cytotoxic activity at 1mg/mL(IC50 =555.70 µg/mL) against HeLa cells. The oils exhibited no significant antioxidant activity (IC50 >1 000 µg/mL) with <100 mg/g GAE of total phenol. The essential oils showed different degrees of activities against Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and Klebsiella pneumoniae (ATCC 314588) at 10 µg/mL, 5 µg/mL and 2.5 µg/mL. These results might provide a future reference basis for further exploration of more of its medicinal application.

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.

Laxative Activities of 80% Methanolic Extract of the Leaves of Grewia ferruginea Hochst Ex A Rich in Mice.

BACKGROUND: There are numerous medicinal plants including the leaves of Grewia ferruginea used as traditional medicine for the treatment of constipation. This study was conducted to evaluate the laxative activity of the leaves of G ferruginea. METHODS: The laxative activity of the leaves of G ferruginea was tested using 3 models: laxative activity, gastrointestinal motility, and gastrointestinal secretion tests. The effect of the plant extract on mean number of feces, fecal water content, ratio of intestinal distance traveled by the charcoal meal and intestinal fluid accumulation were evaluated and analyzed. RESULTS: Significant increase was observed in the mean weight of wet fecal matter at 200 (1.00 ± 0.03 g, P < .05) and 400 mg/kg (1.01 ± 0.02 g, P < .01), relative to loperamide constipated negative control group. Similarly, percent fecal water content was significantly improved in extract treated groups at 100 mg/kg (52.10% ± 2.04%, P < .05), 200 mg/kg (54.02% ± 2.15%, P < .01), and 400 mg/kg (54.25% ± 2.50%, P < .01) compared with the negative control group. The gastroinestinal transit ratio was also significantly increased with 200 mg/kg (P < .01) and 400 mg/kg (P < .001) of the extract relative to the constipated negative control. The crude extract showed significant increase in intestinal fluid accumulation at 200 mg/kg (0.48 ± 0.07 g, P < .05) and 400 mg/kg (0.51 ± 0.08 g, P < .01) compared with the negative control. CONCLUSION: The results of the present study indicated that 80% methanol extract of the leaves of G ferruginea possessed significant laxative activity. As such, this study corroborates the traditional claim of using G ferruginea in the treatment of constipation.

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.

Nutraceutical perspectives and value addition of phalsa (Grewia asiatica L.): A review.

Phalsa (Grewia asiatica L.) is a food plant originating from Southeast Asia, and is cultivated primarily for its fruit. Phalsa fruit is consumed raw or used as a drink or food additive. Additionally, in vitro and in vivo studies have found that extracts from various parts of phalsa plants (especially the fruit) possess strong antioxidant, radioprotective, antimicrobial, antidiabetic, anti-inflammatory, anticancer, and cardio-protective properties. However, despite the identification of numerous nutritional and health benefits of phalsa, research into nutraceutical applications of the plant are somewhat limited. Therefore, the objective of this review was to explore the pharmacological, nutritional, phytochemical, and other potential uses of the phalsa plant. Recommendations for food scientists, nutritionists, and members of other allied disciplines are provided to help direct future research into the production, value addition, preservation, and phytochemical characterization of phalsa. Moreover, its potential health benefits are highlighted, along with the underlying mechanisms of action. PRACTICAL APPLICATIONS: The aim of the present review is to explore functional aspects of phalsa (Grewia asiatica L.) bioactive compounds, their role in improving health, as well as their possible application as a functional food ingredient.

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.