Phytochemical analysis, radical scavenging and glioblastoma U87 cells toxicity studies of stem bark of buckthorn (Rhamnus pentapomica R. Parker).

BACKGROUND: During the past two decades, the correlation between oxidative stress and a variety of serious illnesses such as atherosclerosis, chronic obstructive pulmonary disease (COPD), Alzheimer disease (AD) and cancer has been established. Medicinal plants and their derived phytochemicals have proven efficacy against free radicals and their associated diseases. The current work was aimed to evaluate the phytochemical constituents of Rhamnus pentapomica R. Parker via Gas Chromatography-Mass Spectrometry (GC-MS) and its antioxidant and anti-glioblastoma potentials. METHODS: The bioactive compounds were analysed in Rhamnus pentapomica R. Parker stem bark extracts by GC-MS analysis, and to evaluate their antioxidant and anti-glioblastoma effects following standard procedures. The stem bark was extracted with 80% methanol for 14 days to get crude methanolic extract (Rp.Cme) followed by polarity directed fractionation using solvents including ethyl acetate, chloroform, butanol to get ethyl acetate fraction (Rp.EtAc), chloroform fraction (Rp.Chf) and butanol fraction (Rp.Bt) respectively. Antioxidant assay was performed using DPPH free radicals and cell viability assay against U87 glioblastoma cancer cell lines was performed via MTT assay. RESULTS: In GC-MS analysis, thirty-one compounds were detected in Rp.Cme, 22 in Rp.Chf, 24 in Rp.EtAc and 18 compounds were detected in Rp.Bt. Among the identified compounds in Rp.Cme, 9-Octadecenoic acid (Z)-methyl ester (7.73%), Octasiloxane (5.13%) and Heptasiloxane (5.13%), Hexadecanoic acid, methyl ester (3.76%) and Pentadecanoic acid, 14-methyl-, methyl Ester (3.76%) were highly abundant.. In Rp.Chf, Benzene, 1,3-dimethyl- (3.24%) and in Rp.EtAc Benzene, 1,3-dimethyl-(11.29%) were highly abundant compounds. Antioxidant studies revealed that Rp.Cme and Rp.EtAc exhibit considerable antioxidant potentials with IC50 values of 153.53 µg/ml and 169.62 µg/ml respectively. Both fractions were also highly effective against glioblastoma cells with IC50 of 147.64 µg/ml and 76.41ug/ml respectively. CONCLUSION: Phytochemical analysis revealed the presence of important metabolites which might be active against free radicals and glioblastoma cells. Various samples of the plant exhibited considerable antioxidant and anti-glioblastoma potentials warranting further detailed studies.

2-Hydroxybenzohydrazide as a novel potential candidate against nociception, inflammation, and pyrexia: in vitro, in vivo, and computational approaches.

The current study was designed to evaluate the 2-hydroxybenzohydrazide (HBH) as a drug having efficacy against pyrexia, inflammation, and nociception. Besides, the therapeutic effects of HBH on oxidative stress and C-reactive proteins were also evaluated. The pharmacological studies on HBH (20-60 mg/kg) were conducted using nociception, inflammation, and pyrexia standard models. Naloxone antagonism was performed to assess the possible involvement of opioidergic mechanisms. The antioxidant study was conducted on ABTS and DPPH assays using gallic acid as a standard. Moreover, the binding capability of HBH with enzymes cyclooxygenase-I/II (COX-I/II) was determined using molecular modeling analysis. The findings indicated that the HBH dose-dependently inhibited pain, inflammation, and pyrexia. The HBH has significant anti-nociceptive and anti-inflammatory activities at 60 mg/kg (***p < 0.001), similar to the lower doses of diclofenac sodium (50 mg/kg) and tramadol (30 mg/kg). The HBH at 60 mg/kg reduced pyrexia as paracetamol (150 mg/kg). The HBH at 20-60 mg/kg doses declined the plasma C-reactive protein concentration. The mechanistic studies showed that the anti-nociceptive effect of HBH was antagonized by naloxone, indicating that the opioidergic mechanisms are involved. Furthermore, computational studies showed that the HBH exhibited an affinity for COX-I/II target receptors. The HBH significantly inhibited ABTS and DPPH radicals (IC50 = 33.81 and 26.74 µg/ml). These results proposed that the HBH has significant antipyretic, anti-inflammatory, and anti-nociceptive activities involving opioidergic mechanism.

Neuroprotective evaluation of diospyrin against drug-induced Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease linked to memory impairment. A current investigation was performed to assess the neuroprotective effect of Diospyrin, a novel therapeutic agent, for the curing of Alzheimer's disease. For this purpose, in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays and antioxidant studies were conducted, whereas in-vivo studies involved different behavioral animal models tests such as elevated plus maze (EPM), morris water maze (MWM) and paddling Y-maze test. Results of the in-vitro analysis showed IC50 values of 95 µg/mL for AChE and 110 µg/mL for BChE as compared to the standard drug donepezil (IC50: 95 & 85 µg/mL, respectively). DPPH antioxidant assay showed a maximum of 72.85% inhibition (IC50: 139.74 µg/mL) of DPPH-free radicals at the highest concentration of 1000 µg/mL as compared to the ascorbic acid (IC50: 13.72 µg/mL). Moreover, the in-vivo analysis revealed that diospyrin treatment demonstrated gradual betterment in memory and enhanced motor functionality. On the other hand, the computational analysis also showed that the diospyrin had exceptional binding affinities for both AChE and BChE enzymes. In the net shell, it may be deduced that our compound diospyrin could be a valuable drug candidate in managing neurodegenerative disorders like AD.

Cassia artemisiodes attenuates nociceptive and diabetes-induced neuropathic pain modalities apropos antioxidant and anti-inflammatory mechanisms.

Cassia plants have a considerable position in conventional systems of medicine. The possible anti-nociceptive, anti-inflammatory, and anti-neuropathic properties of Cassia artemisiodes (CAD) extract were tested using the standard animal models. In this study, in vitro antioxidant, cyclooxygenase (COX-1 and 2), and 5-lipoxygenase (5-LOX) inhibitory assays were performed. The anti-inflammatory activity was evaluated using carrageenan, histamine, and serotonin-induced paw edema models. Antipyretic activity, thermally and chemically-induced nociception, and naloxone antagonistic activities were carried out. The CAD extract was tested for anti-neuropathic activity in the streptozotocin-induced diabetic neuropathy model. Suppressing the effect of CAD extract on the mRNA level of inducible nitric oxide synthase (iNOS), COX-2, and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) was determined by performing RT-PCR. The CAD extract inhibited COX-2 and 5-LOX enzymes, paw inflammation, and reduced nociceptive behaviors. The mRNA gene expression of iNOS, COX-2, and inflammatory cytokines was reduced significantly with increased DPPH scavenging activity. The extract significantly reduced the diabetes-induced neuropathic pain. In a nutshell, these results recommended that the CAD extract has anti-nociceptive and anti-neuropathic activities due to inhibition of inflammatory and oxidative signaling.

Mechanistic evaluation of a novel cyclohexenone derivative's functionality against nociception and inflammation: An in-vitro, in-vivo and in-silico approach.

The synthesis of a novel cyclohexanone derivative (CHD; Ethyl 6-(4-metohxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate) was described and the subsequent aim was to perform an in vitro, in vivo and in silico pharmacological evaluation as a putative anti-nociceptive and anti-inflammatory agent in mice. Initial in vitro studies revealed that CHD inhibited both cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymes and it also reduced mRNA expression of COX-2 and the pro-inflammatory cytokines TNF-α and IL-1ß. It was then shown that CHD dose dependently inhibited chemically induced tonic nociception in the abdominal constriction assay and also phasic thermal nociception (i.e. anti-nociception) in the hot plate and tail immersion tests in comparison with aspirin and tramadol respectively. The thermal test outcomes indicated a possible moderate centrally mediated anti-nociception which, in the case of the hot plate test, was pentylenetetrazole (PTZ) and naloxone reversible, implicating GABAergic and opioidergic mechanisms. CHD was also effective against both the neurogenic and inflammatory mediator phases induced in the formalin test and it also disclosed anti-inflammatory activity against the phlogistic agents, carrageenan, serotonin, histamine and xylene compared with standard drugs in edema volume tests. In silico studies indicated that CHD possessed preferential affinity for GABAA, opioid and COX-2 target sites and this was supported by molecular dynamic simulations where computation of free energy of binding also favored the formation of stable complexes with these sites. These findings suggest that CHD has prospective anti-nociceptive and anti-inflammatory properties, probably mediated through GABAergic and opioidergic interactions supplemented by COX-2 and 5-LOX enzyme inhibition in addition to reducing pro-inflammatory cytokine expression. CHD may therefore possess potentially beneficial therapeutic effectiveness in the management of inflammation and pain.

Synthetic ß-hydroxy ketone derivative inhibits cholinesterases, rescues oxidative stress and ameliorates cognitive deficits in 5XFAD mice model of AD.

Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new anti-AD remedies, 2-[Hydroxy-(4-nitrophenyl)methyl]-cyclopentanone (NMC), a ß hydroxyl ketone derivative was studied to explore its neuroprotective potentials against AD. The in-vitro AChE and BuChE enzymes inhibition were evaluated by Ellman protocol and antioxidant potentials of NMC by DPPH free radical scavenging assay. In-vivo behavioral studies were performed in the transgenic 5xFAD mice model of AD using shallow water maze (SWM), Paddling Y-Maze (PYM), elevated plus maze (EPM) and balance beam (BB) tests. Also, the ex-vivo cholinesterase inhibitory effects of NMC and histopathological analysis of amyloid-ß plaques were determined in the frontal cortex and hippocampal regions of the mice brain. NMC exhibited significant in vitro anti-cholinesterase enzyme potentials with an IC50 value of 67 µg/ml against AChE and 96 µg/ml against BuChE respectively. Interestingly, the activities of AChE and BuChE enzymes were also significantly lower in the cortex and hippocampus of NMC-treated groups. Also, in the DPPH assessment, NMC displayed substantial antioxidant properties with an IC50 value observed as 171 µg/ml. Moreover, histopathological analysis via thioflavin-s staining displayed significantly lower plaques depositions in the cortex and hippocampus region of NMC-treated mice groups. Furthermore, SWM, PYM, EPM, and BB behavioral analysis indicated that NMC enhanced spatial learning, memory consolidation and improved balance performance. Altogether, to the best of our knowledge, we believe that NMC may serve as a potential and promising anti-cholinesterase, antioxidant and neuroprotective agent against AD.

Neuroprotective effect of Bacopa monnieri against morphine-induced histopathological changes in the cerebellum of rats.

Opioid addiction is associated with oxidative cell injury in neuronal cells. In this study, Bacopa monnieri (L.), a reputed nootropic plant, was evaluated against morphine-induced histopathological changes in the cerebellum of rats. B. monnieri methanolic extract (mBME) (40 mg/kg, p.o) and ascorbic acid (50 mg/kg, i.p) were administered two hours before morphine (20 mg/kg, i.p) for 14 and 21 days. The in vitro antioxidant activity of mBME was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging assay. Morphine produced vacuolization of basket and stellate cells and reduced the size of Purkinje cells in the cerebellum after 14 days. However, treatment for 21 days was associated with severe shrinkage of Purkinje cells with loss of their characteristic flask-shaped appearance as well as degeneration of basket, stellate and granule cells. Pretreatment with mBME and ascorbic acid for 14 and 21 days attenuated the morphine-induced histopathological changes in the cerebellum. The EC50 for the DPPH free-radical scavenging assay of mBME (39.06 µ/mL) as compared to ascorbic acid (30.25 µ/mL) and BHT (34.34 µ/mL) revealed that mBME strongly scavenged the free-radicals and thus possessed an efficient antioxidant propensity. These results concluded that B. monnieri having strong antioxidant activity exerted a protective effect against morphineinduced cerebellar toxicity.

Synthetic and natural antioxidants attenuate cisplatin-induced vomiting.

BACKGROUND: Synthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which also possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy. In this study, synthetic [N-(2-mercaptopropionyl) glycine (MPG), vitamin C (Vit-C)] and natural [grape seed proanthocyanidin (GP), B. monnieri n-butanolic fraction (BM-ButFr)] antioxidants and their combinations were evaluated against cisplatin-induced emesis in pigeons during a 24 h observation period. METHODS: Emesis was induced using cisplatin (7.0 mg/kg, i.v). MPG (10, 20, 30 mg/kg), Vit-C (100, 200, 300 mg/kg), GP (50, 100, 150 mg/kg) and BM-ButFr (5, 10, 20 mg/kg) and their combinations were administered i.m., 15 min before cisplatin administration. The number of vomiting bouts, retching, emetic latency and % weight loss were recorded to assess antiemetic potential. Antioxidant activity was evaluated by the DPPH free radical scavenging assay (FRSA). RESULTS: Significant attenuation of vomiting bouts, retching, % weight loss along with an increase in latency was produced by all the antioxidants and their combinations compared to cisplatin alone and this is the first report of this activity of GP in pigeons. Low EC50 values in the FRSA for MPG (67.66 µg/mL), Vit-C (69.42 µg/mL), GP (6.498 µg/mL) and BM-ButFr (55.61 µg/mL) compared to BHT standard (98.17 µg/mL) demonstrated their radical scavenging capacity. Correlation between the antioxidant activity and antiemetic efficacy disclosed a high degree of correlation for the tested antioxidants. CONCLUSION: The selected synthetic and natural antioxidants and their combinations were able to attenuate cisplatin-induced vomiting, which correlated with their potent in vitro antioxidant activity.

Molecularly Characterized Solvent Extracts and Saponins from Polygonum hydropiper L. Show High Anti-Angiogenic, Anti-Tumor, Brine Shrimp, and Fibroblast NIH/3T3 Cell Line Cytotoxicity.

Polygonum hydropiper is used as anti-cancer and anti-rheumatic agent in folk medicine. This study was designed to investigate the anti-angiogenic, anti-tumor, and cytotoxic potentials of different solvent extracts and isolated saponins. Samples were analyzed using GC, Gas Chromatography-Mass Spectrometry (GC-MS) to identify major and bioactive compounds. Quantitation of antiangiogenesis for the plant's samples including methanolic extract (Ph.Cr), its subsequent fractions; n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq), saponins (Ph.Sp) were performed using the chick embryo chorioallantoic membrane (CAM) assay. Potato disc anti-tumor assay was performed on Agrobacterium tumefaciens containing tumor inducing plasmid. Cytotoxicity was performed against Artemia salina and mouse embryonic fibroblast NIH/3T3 cell line following contact toxicity and MTT cells viability assays, respectively. The GC-MS analysis of Ph.Cr, Ph.Hex, Ph.Chf, Ph.Bt, and Ph.EtAc identified 126, 124, 153, 131, and 164 compounds, respectively. In anti-angiogenic assay, Ph.Chf, Ph.Sp, Ph.EtAc, and Ph.Cr exhibited highest activity with IC50 of 28.65, 19.21, 88.75, and 461.53 µg/ml, respectively. In anti-tumor assay, Ph.Sp, Ph.Chf, Ph.EtAc, and Ph.Cr were most potent with IC50 of 18.39, 73.81, 217.19, and 342.53 µg/ml, respectively. In MTT cells viability assay, Ph.Chf, Ph.EtAc, Ph.Sp were most active causing 79.00, 72.50, and 71.50% cytotoxicity, respectively, at 1000 µg/ml with the LD50 of 140, 160, and 175 µg/ml, respectively. In overall study, Ph.Chf and Ph.Sp have shown overwhelming results which signifies their potentials as sources of therapeutic agents against cancer.

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms.

BACKGROUND: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. METHODS: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. RESULTS: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency. CONCLUSIONS: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed.

Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.

BACKGROUND: Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. METHODS: Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. RESULTS: Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. CONCLUSION: The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation of its antiemetic effect.

Nature cures nature: Hypericum perforatum attenuates physical withdrawal signs in opium dependent rats.

CONTEXT: Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs. AIM: To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome. MATERIALS AND METHODS: The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group. RESULTS: Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p < 0. 05) and (F(2, 24) = 3.689, p < 0.05), respectively. The plant extract in the acutely treated group reduced diarrhea (F(2, 24) = 4.850, p < 0. 05 vs. saline). It decreased rectal temperature by chronic treatment at 30 min (F(2, 24) = 4.88, p < 0.05), 60 min (F(2, 240 = 5.364, p < 0.01) and 120 min (F(2, 24) = 4.907, p < 0.05). DISCUSSION AND CONCLUSION: This study reveals that the extract of Hypericum perforatum attenuates some physical signs of opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

Comparative evaluation of gastroulcerogenic potential of nitrogen isoforms of salicyl alcohol and aspirin in rats: biochemical and histological study.

The aim of the current study was to explore in vivo any relative gastroulcerogenic prospective propensity of newly synthesized nitrogen containing derivatives of salicyl alcohol; compound (I) [1-(2-hydroxybenzyl)piperidinium chloride], compound (II) [4-carbamoyl-1-(2-hydroxybenzyl)piperidinium chloride] and aspirin in albino rats. The experimental groups received the following oral treatments daily for 6 days: group I saline control; group II, standard (aspirin) treatment group [150 mg/kg of body weight]; group III, test (compound I) treatment group [100, 150 mg/kg]; group IV, test (compound II) treatment group [100, 150 mg/kg]. The results showed that in the case of the aspirin treated group and compound (I) [150 mg/kg], there was a significant increase in gastric volume, free acidity, total acidity, ulcer score and a decrease in gastric pH. Furthermore, histopathological examination of gastric mucosa of these treated groups revealed detectable morphological changes. Utilizing the same protocol, synthetic compound (I) [100 mg/kg] and (II) [100, 150 mg/kg] exhibited no statistically significant ulcerogenic or cytotoxic properties. A cyclooxygenase (COX) selectivity test indicated the preferential inhibition of COX-I and COX-II enzymes by compounds (I) and (II). This study therefore indicates that these synthetic compounds may possess reduced ulcerogenic potential and could be a functional substitute to aspirin.

Inhibitory effect of bacopasides on spontaneous morphine withdrawal induced depression in mice.

Bacopa monnieri is a perennial herb with a world known image as a nootropic. We investigated the effect of Bacopa monnieri methanolic extract (Mt Ext BM) 10, 20, and 30 mg/kg body weight (b.w) on acquisition and expression of morphine withdrawal induced depression in mice. Locally available Bacopa monnieri (BM) was screened for contents of Bacoside A3, Bacopasaponin C, and Bacopaside II using HPLC with UV. Morphine dependence was induced in mice using twice daily escalating chronic morphine treatments (20-65 mg/kg b.w) for eight consecutive days. Morphine withdrawal induced depression was assayed in animals using forced swimming test (FST), three days after last morphine injection. The HPLC analysis revealed that Mt-ext BM contained Bacoside A3 as major component, i.e. 4 µg in each mg of extract. The chronic treatment with Met Ext BM 10, 20, and 30 mg/kg b.w. dosing significantly inhibited opioid withdrawal induced depression in mice. These findings imply a newer potential role of Bacopa monnieri in the clinical management of opioid withdrawal induced depression which can be attributed to Bacoside A3.

Pistagremic acid, a glucosidase inhibitor from Pistacia integerrima.

Pistacia integerrima Stewart in traditionally used as folk remedy for various pathological conditions including diabetes. In order to identify the bioactive compound responsible for its folk use in diabetes, a phytochemical and biological study was conducted. Pistagremic acid (PA) was isolated from the dried galls extract of P. integerrima. Strong α-glucosidase inhibitory potential of PA was predicted using its molecular docking simulations against yeast α-glucosidase as a therapeutic target. Significant experimental α-glucosidase inhibitory activity of PA confirmed the computational predictions. PA showed potent enzyme inhibitory activity both against yeast (IC(50): 89.12±0.12µM) and rat intestinal (IC(50): 62.47±0.09µM) α-glucosidases. Interestingly, acarbose was found to be more than 12 times more potent an inhibitor against mammalian (rat intestinal) enzyme (having IC(50) value 62.47±0.09µM), as compared to the microbial (yeast) enzyme (with IC(50) value 780.21µM). Molecular binding mode was explored via molecular docking simulations, which revealed hydrogen bonding interactions between PA and important amino acid residues (Asp60, Arg69 and Asp 70 (3.11Å)), surrounding the catalytic site of the α-glucosidase. These interactions could be mainly responsible for their role in potent inhibitory activity of PA. PA has a strong potential to be further investigated as a new lead compound for better management of diabetes.