Opuntia monacantha: Validation of the anti-inflammatory and anti-arthritic activity of its polyphenolic rich extract in silico and in vivo via assessment of pro- and anti-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to treat pain and inflammation. O. monacantha cladodes showed pharmacological effects such as antioxidant potential owing to the presence of certain polysaccharides, flavonoids, and phenols. AIM OF THE STUDY: This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM). MATERIALS AND METHODS: In vivo edema in rat paw was triggered by carrageenan and used to evaluate anti-inflammatory activity, while induction of arthritis by Complete Freund's Adjuvant (CFA) rat model was done to measure anti-arthritic potential. In silico studies of the previously High performance liquid chromatography (HPLC) characterized metabolites of ethanol extract was performed by using Discovery Studio 4.5 (Accelrys Inc., San Diego, CA, USA) within active pocket of glutaminase 1 (GLS1) (PDB code: 3VP1; 2.30 Å). RESULTS: EOM, particularly at 750 mg/kg, caused a reduction in the paw edema significantly and decreased arthritic score by 80.58% compared to the diseased group. It revealed significant results when histopathology of ankle joint was examined at 28th day as it reduced inflammation by 18.06%, bone erosion by 15.50%, and pannus formation by 24.65% with respect to the diseased group. It restored the altered blood parameters by 7.56%, 18.47%, and 3.37% for hemoglobin (Hb), white blood count (WBC), and platelets, respectively. It also reduced rheumatoid factor RF by 13.70% with concomitant amelioration in catalase (CAT) and superoxide dismutase (SOD) levels by 19%, and 34.16%, respectively, in comparison to the diseased group. It notably decreased mRNA expression levels of COX-2, IL-6, TNF-α, IL-1, NF-κß and augmented the levels of IL-4 and IL-10 in real time PCR with respect to the diseased group and piroxicam. HPLC analysis previously performed showed that phenolic acids and flavonoids are present in E-OM. Molecular docking studies displayed pronounced inhibitory potential of these compounds towards glutaminase 1 (GLS1), approaching and even exceeding piroxicam. CONCLUSIONS: Thus, Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals.

HPLC and GC Characterization of Dicliptera bupleuroides Aerial Parts and Evaluation of Its Anti-Inflammatory Potential in Vitro, in silico and in Vivo Using Carrageenan and Formalin Induced Inflammation in Rat Models.

The current study aimed to evaluate the anti-inflammatory activity of Dicliptera bupleuroides Nees aerial parts methanol extract and its different fractions namely hexane, chloroform, ethyl acetate and butanol in vitro using cyclooxygenase inhibitory assay (COX-2). In vivo anti-inflammatory evaluation was performed using carrageenan and formalin induced inflammation in rat models followed by molecular docking. High performance liquid chromatography (HPLC) and gas chromatography coupled with mass chromatography (GC/MS) analyses were used for chemical analyses of the tested samples. The tested samples showed significant inhibition in COX-2 inhibitory assay where methanol extract (DBM) showed the highest inhibitory potential at 100 µg/mL estimated by 67.86 %. At a dose of 400 mg/kg, all of the examined samples showed pronounced results in carrageenan induced acute inflammation in rat model at 4th h interval with DBM showed the highest efficiency displaying 65.32 % inhibition as compared to the untreated rats. Formalin model was employed for seven days and DBM exhibited 65.33 % and 69.39 % inhibition at 200 and 400 mg/kg, respectively approaching that of the standard on the 7th day. HPLC revealed the presence of caffeic acid, gallic acid and sinapic acid, quercetin and myricetin in DBM. GC/MS analysis of its hexane fraction revealed the presence of 16 compounds belonging mainly to fatty acids and sterols that account for 85.26 % of the total detected compounds. Molecular docking showed that hexadecanoic acid followed by decanedioic acid and isopropyl myristate showed the best fitting within cyclooxygenase-II (COX-II) while nonacosane followed by hexatriacontane and isopropyl myristate revealed the most pronounced fitting within the 5-lipoxygenase (5-LOX) active sites. Absorption, metabolism, distribution and excretion and toxicity prediction (ADMET/ TOPKAT) concluded that most of the detected compounds showed reasonable pharmacokinetic, pharmacodynamic and toxicity properties that could be further modified to be more suitable for incorporation in pharmaceutical dosage forms combating inflammation and its undesirable consequences.

Phytochemical and biological studies of Panicum antidotale aerial parts ethanol extract supported by molecular docking study.

Panicum antidotale has traditionally been used as a poultice to alleviate local inflammation and painful diseases. This study aimed to evaluate the anti-inflammatory, wound-healing, analgesic, and antipyretic potential of its ethanol extract (PAAPEE) in vivo for the first time. In vitro antioxidant assays of Panicum antidotale using a 2,2-diphenyl-1-picrylhydrazyl assay revealed that it showed IC50 of 62.50 ± 6.85 µg/mL in contrast to standard, ascorbic acid, that showed IC50 of 85.51 ± 0.38 µg/mL. Administration of PAAPEE at a dose of 500 mg/kg (PAAPEE-500) displayed 78.44% and 75.13% inhibition of paw edema in carrageenen and histamine-induced edema models. respectively, 6 h post-treatment compared to that of the untreated group. Furthermore, it showed 68.78% inhibition of Freund's complete adjuvant-induced edema 21 days after treatment. It reduced the animal's rectal temperature in the yeast-induced fever model to 99.45 during the fourth h post-treatment. It significantly inhibited abnormal writhing by 44% in the acetic acid-induced pain model. PAE-500 also showed enhancement in wound closure by 72.52% with respect to that of the untreated group on the 10th day post-treatment using the excision healing of wound model. Histopathological examination of skin samples confirmed this improvement, showing enhanced tissue architecture with minimal infiltration of inflammatory cells. High-performance liquid chromatography (HPLC) of PAAPEE revealed the presence of quercetin, gallic, p-coumaric, benzoic, chlorogenic, syringic, ferulic, cinnamic, and sinapic acids. Molecular docking of 5-lipoxygenase and glycogen synthase kinase-3 ß protein indicated their potential interaction within the active sites of both enzymes. Thus, P. antidotale serves as an effective natural wound-healing, anti-inflammatory, analgesic, and antipyretic agent.

GC-MS Chemical Profiling, Biological Investigation of Three Salvia Species Growing in Uzbekistan.

Salvia is a potentially valuable aromatic herb that has been used since ancient times. The present work studied the chemical profile of three Salvia species essential oils (EO): S. officinalis, S. virgata and S. sclarea, as well as assessing their antioxidant and enzyme inhibitory activities. A total of 144 compounds were detected by GC-MS analysis, representing 91.1, 84.7 and 78.1% in S. officinalis, S. virgata and S. sclarea EOs, respectively. The major constituents were cis-thujone, 2,4-hexadienal and 9-octadecenoic acid, respectively. The principal component analysis (PCA) score plot revealed significant discrimination between the three species. The antioxidant activity of the EOs was evaluated using in vitro assays. Only S. virgata EO showed antioxidant activity in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay (26.6 ± 1.60 mg Trolox equivalent (TE)/g oil). Moreover, this oil exhibited the highest antioxidant activity in 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric-reducing antioxidant capacity (CUPRAC) and ferric-reducing power (FRAP) assays in comparison with the other two EOs (190.1 ± 2.04 vs. 275.2 ± 8.50 and 155.9 ± 1.33 mg TE/g oil, respectively). However, S. virgata oil did not show any effect in the chelating ability assay, while in the PBD assay, S. officinalis had the best antioxidant activity (26.4 ± 0.16 mmol TE/g oil). Enzyme inhibitory effect of the EOs was assessed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, α-glucosidase and α-amylase. AChE enzyme was more sensitive to S. officinalis EO (4.2 ± 0.01 mg galantamine equivalent (GALAE)/g oil), rather than S. virgata EO, which was ineffective. However, S. virgata had the highest BChE effect (12.1 ± 0.16 mg GALAE/g oil). All studied oils showed good tyrosinase inhibitory activity, ranging between 66.1 ± 0.61 and 128.4 ± 4.35 mg kojic acid equivalent (KAE)/g oil). Moreover, the EOs did not exhibit any glucosidase inhibition and were weak or inefficient on amylase enzyme. Partial least squares regression (PLS-R) models showed that there is an excellent correlation between the antioxidant activity and the volatile profile when being compared to that of enzyme inhibitory activity. Thus, the studied Salvia essential oils are interesting candidates that could be used in drug discovery for the management of Alzheimer's and hyperpigmentation conditions.

Malva parviflora Leaves and Fruits Mucilage as Natural Sources of Anti-Inflammatory, Antitussive and Gastro-Protective Agents: A Comparative Study Using Rat Models and Gas Chromatography.

Malva parviflora L., Little mallow, has been traditionally used as an alternative food source. It acts as a medicinal herb containing a potential source of mucilage thus herein; we aimed to assess the toxicity, anti-inflammatory, antitussive and gastro-protective actions of M. parviflora mucilage extracted from its leaves (MLM) and fruit (MFM). Toxicity studies were investigated by in vitro hemolytic assay whereas acute anti-inflammatory and antitussive activities were assessed by carrageenan-induced paw edema and sulphur dioxide induced cough model in rats, respectively. Gastro-protective effects were studied using ethanol induced acute and chronic gastric ulcer rat models. Their metabolic profiles were determined using gas chromatography. The results revealed that MLM and MFM were non-toxic towards human erythrocytes and their lethal doses were found to be greater than 5 g/kg. Pretreatment with MLM (500 mg/kg) and MFM (500 mg/kg) significantly reduced the carrageenan-induced paw thickness (p < 0.001). Maximum edema inhibition (%) was observed at 4 h in diclofenac sodium (39.31%) followed by MLM (27.35%) and MFM (15.68%). Animals pretreated with MLM (500 mg/kg) significantly lower the cough frequency in SO2 gas induced cough models in contrast to control. Moreover, MLM at doses of 250 and 500 mg/kg reduced the ethanol induced gastric mucosal injuries in acute gastric ulcer models presenting ulcer inhibition of 23.04 and 38.74%, respectively. The chronic gastric ulcer model MFM (500 mg/kg) demonstrated a remarkable gastro-protective effect showing 63.52% ulcer inhibition and results were closely related to standard drug sucralfate. In both models, MLM and MFM decreased gastric juice volume and total acidity in addition to an increased gastric juice pH and gastric mucous content justifying an anti-secretary role of this mucilage that was further confirmed by histopathological examination. Meanwhile, GC analyses of the mucilage revealed their richness with natural as well as acidic monosaccharides. It is concluded that MLM and MFM can be used therapeutically for the management of inflammation, cough and gastric ulcer.

Malva parviflora Leaves Mucilage: An Eco-Friendly and Sustainable Biopolymer with Antioxidant Properties.

Malva parviflora L. is an edible and medicinal herb containing mucilaginous cells in its leaves. Mucilage obtained from M. parviflora leaves (MLM) was extracted in distilled water (1:10 w/v) at 70 °C followed by precipitation with alcohol. Preliminary phytochemical tests were performed to assess the purity of the extracted mucilage. Results showed that the yield of mucilage was 7.50%, and it was free from starch, alkaloids, glycosides, saponins, steroids, lipids and heavy metals. MLM had 16.19% carbohydrates, 13.55% proteins and 4.76% amino acids, which indicate its high nutritional value. Physicochemical investigations showed that MLM is neutral and water-soluble, having 5.84% moisture content, 15.60% ash content, 12.33 swelling index, 2.57 g/g water-holding capacity and 2.03 g/g oil-binding capacity. The functional properties, including emulsion capacity, emulsion stability, foaming capacity and stability increased with increased concentrations. Micromeritic properties, such as bulk density, tapped density, Carr's index, Hausner ratio, and angle of repose, were found to be 0.69 g/cm3, 0.84 g/cm3, 17.86%, 1.22 and 28.5, respectively. Scanning electron microscopy (SEM) showed that MLM is an amorphous powder possessing particles of varying size and shape; meanwhile, rheological studies revealed the pseudoplastic behavior of MLM. The thermal transition process of MLM revealed by a differential scanning calorimetry (DSC) thermogram, occurring at a reasonable enthalpy change (∆H), reflects its good thermal stability. The presence of functional groups characteristic of polysaccharides was ascertained by the infrared (IR) and gas chromatography/mass spectrometry (GC/MS) analyses. GC revealed the presence of five neutral monosaccharides; namely, galactose, rhamnose, arabinose, glucose and mannose, showing 51.09, 10.24, 8.90, 1.80 and 0.90 mg/g of MLM, respectively. Meanwhile, galacturonic acid is the only detected acidic monosaccharide, forming 15.06 mg/g of MLM. It showed noticeable antioxidant activity against the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical with an IC50 value of 154.27 µg/mL. It also prevented oxidative damage to DNA caused by the Fenton reagent, as visualized in gel documentation system. The sun protection factor was found to be 10.93 ± 0.15 at 400 µg/mL. Thus, MLM can be used in food, cosmetic and pharmaceutical industry and as a therapeutic agent due to its unique properties.

Overcoming Tribal Boundaries: The Biocultural Heritage of Foraging and Cooking Wild Vegetables among Four Pathan Groups in the Gadoon Valley, NW Pakistan.

The foraging and consumption of wild food plants is a long-standing tradition in many parts of the world and their importance in promoting food security has become more widely debated in recent years. The current study aimed to document, analyze, and interpret the traditional knowledge of non-cultivated vegetables among four Pathan tribes (Alisher Khel, Hadarzai, Haji Khel, and Umarzai) living in the Gadoon Valley, Swabi District, Khyber Pakhtunkhwa, NW Pakistan, and to evaluate how these practices vary among the considered tribal communities. A total of 104 informants were interviewed via a semi-structured, open-ended questionnaire and group discussions. The field survey was conducted from October 2018 to November 2020. Information about local names, growth habit, used plant parts, food/cooking details, medicinal perceptions, availability season, and market prices were collected. The field survey recorded 51 non-cultivated vegetables belonging to 24 botanical families, for which the frequently used plant parts included young leaves, stems, and flowers. The greatest number of use reports was recorded for Colocasia and the highest cultural index value was recorded for Rumex dentatus; the dominant botanical families were Asteraceae and Fabaceae (six species each). Seven species were found to be sold at local and regional markets. Cross-cultural analysis among the four considered tribes showed that the largest number of species was reported by members of the Hadarzai and Umarzai tribes, although most of the quoted wild vegetables were homogenously gathered among all considered communities, with some more idiosyncratic plant uses among the Umarzai group, who have likely been less affected by the erosion of traditional knowledge or possibly have had less access to traded cultivated vegetables. The novelty of the data was assessed by comparing it with the previously published wild food ethnobotanical literature of Pakistan, which showed fifteen new wild vegetables not yet reported in the NW of the country. The recorded food biocultural heritage should be seriously considered in future local development projects aimed at fostering environmental sustainability and food security.

Jojoba Oil: An Updated Comprehensive Review on Chemistry, Pharmaceutical Uses, and Toxicity.

Jojoba is a widely used medicinal plant that is cultivated worldwide. Its seeds and oil have a long history of use in folklore to treat various ailments, such as skin and scalp disorders, superficial wounds, sore throat, obesity, and cancer; for improvement of liver functions, enhancement of immunity, and promotion of hair growth. Extensive studies on Jojoba oil showed a wide range of pharmacological applications, including antioxidant, anti-acne and antipsoriasis, anti-inflammatory, antifungal, antipyretic, analgesic, antimicrobial, and anti-hyperglycemia activities. In addition, Jojoba oil is widely used in the pharmaceutical industry, especially in cosmetics for topical, transdermal, and parenteral preparations. Jojoba oil also holds value in the industry as an anti-rodent, insecticides, lubricant, surfactant, and a source for the production of bioenergy. Jojoba oil is considered among the top-ranked oils due to its wax, which constitutes about 98% (mainly wax esters, few free fatty acids, alcohols, and hydrocarbons). In addition, sterols and vitamins with few triglyceride esters, flavonoids, phenolic and cyanogenic compounds are also present. The present review represents an updated literature survey about the chemical composition of jojoba oil, its physical properties, pharmacological activities, pharmaceutical and industrial applications, and toxicity.

Pimenta dioica and Pimenta racemosa: GC-based metabolomics for the assessment of seasonal and organ variation in their volatile components, in silico and in vitro cytotoxic activity estimation.

Volatile constituents isolated from the stems (S) and leaves (L) of Pimenta dioica (PD) and Pimenta racemosa (PR) during the four seasons were analyzed using GLC/FID (Gas liquid chromatography - flame ionization detector) and GLC/MS (Gas liquid chromatography - mass spectrometry). Eighty-nine compounds were identified in all samples, in which oxygenated monoterpene represented by eugenol was the major constituent in PDS-S3 (autumn) (88.71%) and PDS-S2 (summer) (88.41%). Discrimination between P. dioica and P. racemosa leaves and stems in different seasons was achieved by applying chemometrics analysis comprising Principal Component Analysis (PCA) and Hierarchal Cluster Analysis (HCA). For P. dioica, they were partially segregated where leaves collected from spring and autumn were superimposed, and similarly for P. dioica stems collected in summer and autumn. For P. racemosa leaves, the PCA score plot showed that all seasons were completely segregated from each other, with the winter and autumn samples being in very close distance to each other. P. racemosa stems collected in autumn and spring exhibited significant variation, as they were completely detached from each other. Moreover, summer and winter fell in a near distance to each other. An in vitro cell viability assay was done to evaluate the variation in the cytotoxicity of the isolated essential oils against breast (MCF-7), hepatic (HepG-2), and cervical (HeLa-2) cancer cell lines using the MTT assay. The maximum cytotoxic effect was observed by PDL against HeLa, HepG-2 and MCF-7 cells with IC50 values equal to 122.1, 139.6, and 178.7 µg mL-1, respectively. An in silico study was done to assess the cytotoxic effect of the major compounds detected in the oils by determining their inhibitory effect on human DNA topoisomerase II (TOP-2), human cyclin-dependent kinase 2 (CDK-2) and matrix metalloproteinase 13 (MMP-13). o-Cymene followed by eugenol showed the highest fitting with all of the examined proteins approaching doxorubicin. It can be concluded that GC coupled with chemometrics provide a strong tool for the discrimination of samples, while Pimenta could afford a natural drug that could alleviate cancer.

Sugar Containing Compounds and Biological Activities of Lagochilus setulosus.

Phytochemical investigation of the methanolic extract obtained from the aerial parts of Lagochilus setulosus (Lamiaceae) afforded the new compound 1-methoxy-3-O-ß-glucopyranosyl-α-l-oliose (1) together with five known glycosides, namely sitosterol-3-O-ß-glucoside (2), stigmasterol-3-O-ß-glucoside (3), pinitol (4), 6ß-hydroxyl-7-epi-loganin (5), and chlorotuberoside (6). The structures of these compounds were elucidated by extensive spectroscopic analyses, especially HR-MS, 1D and 2D NMR spectroscopy. The in vitro cytotoxic activity of the methanolic extract and the isolated compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and crystal violet (CV) staining assays. In addition, the antifungal activities of the components were evaluated against Botrytis cinerea, Septoria tritici, and Phytophthora infestans. The anthelmintic potential was determined against Caenorhabditis elegans nematodes. Neither the extract nor the isolated compounds showed promising activity in all the bioassays.

Cytotoxic Alkaloids Derived from Marine Sponges: A Comprehensive Review.

Marine sponges (porifera) have proved to be a prolific source of unique bioactive secondary metabolites, among which the alkaloids occupy a special place in terms of unprecedented structures and outstanding biological activities. Identification of active cytotoxic alkaloids extracted from marine animals, particularly sponges, is an important strive, due to lack of knowledge on traditional experiential and ethnopharmacology investigations. In this report, a comprehensive survey of demospongian bioactive alkaloids in the range 1987-2020 had been performed with a special emphasis on the potent cytotoxic activity. Different resources and databases had been investigated, including Scifinder (database for the chemical literature) CAS (Chemical Abstract Service) search, web of science, Marin Lit (marine natural products research) database. More than 230 representatives of different classes of alkaloids had been reviewed and classified, different genera belonging to the phylum porifera had been shown to be a prolific source of alkaloidal molecules, including Agelas sp., Suberea sp., Mycale sp., Haliclona sp., Epipolasis sp., Monanchora sp., Crambe sp., Reniera sp., and Xestospongia sp., among others. The sufficient production of alkaloids derived from sponges is a prosperous approach that requires more attention in future studies to consider the constraints regarding the supply of drugs, attained from marine organisms.

The Genus Lagochilus (Lamiaceae): A Review of Its Diversity, Ethnobotany, Phytochemistry, and Pharmacology.

The genus Lagochilus (Lamiaceae) is native to Central, South-Central, and Eastern Asia. It comprises 44 species, which have been commonly used as herbal medicines for the treatments of various ailments for thousands of years, especially in Asian countries. This review aims to summarize the chemical constituents and pharmacological activities of species from the genus Lagochilus to unveil opportunities for future research. In addition, we provide some information about their traditional uses, botany, and diversity. More than 150 secondary metabolites have been reported from Lagochilus, including diterpenes, flavonoids, phenolic compounds, triterpenoids, iridoid glycosides, lignans, steroids, alkaloids, polysaccharides, volatile, non-volatile and aromatic compounds, lipids, carbohydrates, minerals, vitamins, and other secondary metabolites. In vitro and in vivo pharmacological studies on the crude extracts, fractions, and isolated compounds from Lagochilus species showed hemostatic, antibacterial, anti-inflammatory, anti-allergic, cytotoxic, enzyme inhibitory, antispasmodic, hypotensive, sedative, psychoactive, and other activities.

Chemical constituents and gastro-protective potential of Pachira glabra leaves against ethanol-induced gastric ulcer in experimental rat model.

Gastric ulcer is a very common illness that adversely affects a significant number of people all over the globe. Phytochemical investigation of P. glabra leaf alcohol extract (PGLE) resulted in the isolation and Characterization of a new nature compound, quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)-ß -D-galactoside (4), in addition to seven known compounds. They are ferulic acid (1), p- coumaric acid (2), quercetin 3-O-α-L-rhamnoside-3'-O-ß-D-glucoside (3), quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)- ß -Dgalactoside (4), quercetin-3- O-ß -D-galactoside (5), 7-hydroxy maltol-3-O-ß-D-glucoside (6), maltol-3- O-ß -D-glucoside (7), and methyl coumarate (8) that were first to be isolated from the genus Pachira. PGLE demonstrated in vitro anti-Helicobacter pylori activity. Moreover, the in vivo gastroprotective assessment of PGLE at different dosses, 100, 200, and 400 mg/kg against ethanol induced ulceration revealed a dose-dependent gastroprotection comparable to omeprazole. PGLE attenuated gastric lesions and histopathological changes triggered by ethanol. Interestingly, PGLE exhibited an anti-inflammatory effect through down-regulating the expression of nuclear factor-ĸB and pro-inflammatory enzyme cyclooxygenase-2 in the ulcer group. It also hindered apoptosis through decreasing Bax and increasing Bcl-2 expression hence decreasing Bax/Bcl2 ratio with a subsequent reduction in caspase 3 expression. Collectively, P. glabra is a rich reservoir of various phytochemicals reflecting a promising potential for alleviation of gastric ulcer through the mediation of inflammatory and apoptotic cascades.

Pinoresinol-4-O-ß-D-glucopyranoside: a lignan from prunes (Prunus domestica) attenuates oxidative stress, hyperglycaemia and hepatic toxicity in vitro and in vivo.

OBJECTIVES: This study aimed to explore the pharmacological properties of pinoresinol-4-O-ß-D-glucopyranoside (PG), isolated from prunes. METHODS: In-vitro antioxidant activity was assessed using ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) assays. In-vivo hepatoprotective activity was evaluated using CCl4 -induced hepatotoxicity mouse model. The antihyperglycaemic activity was determined in vitro using α-glucosidase and α-amylase inhibiting activity and in vivo using streptozotocin-treated model. Molecular modelling was done on α-amylase, α-glucosidase, aldose reductase and peroxisome proliferator-activated receptor gamma. KEY FINDINGS: Pinoresinol-4-O-ß-D-glucopyranoside showed promising antioxidant activity in FRAP and ABTS assays with total antioxidant capacity equal 418.47 and 1091.3 µmol/g in terms of ascorbic acid, respectively. PG (50 mg/kg b.w.) exhibited a hepatoprotective activity in vivo as it lowered AST and ALT levels. PG showed a potent in-vitro antihyperglycaemic activity as it inhibited α-glucosidase with an IC50 value of 48.13 µg/ml. PG caused a prominent decline in serum glucose level by 37.83% in streptozotocin-treated mice with promising elevation in insulin level of 25.37%. Oxidative stress markers were reduced by PG, and it showed a high fitting on α-amylase and α-glucosidase active sites. CONCLUSIONS: Pinoresinol-4-O-ß-D-glucopyranoside is a natural entity combating oxidative stress, hepatic damage and diabetes.

New γ-pyrone glycoside from Pachira glabra and assessment of its gastroprotective activity using an alcohol-induced gastric ulcer model in rats.

Pachira glabra is a medium sized tree that is famous for its delicious edible seeds and leaves. Phytochemical investigation of Pachira glabra leaf alcohol extract led to the isolation of a new γ-pyrone glycoside, 7-hydroxy maltol-3-O-ß-d-glucoside (HMGlu). In vivo assessment of the gastro-protective activity of HMGlu demonstrated superior gastro-protection at a dose of 100 mg kg-1, close to the value triggered by the standard reference omeprazole drug (evidenced by morphological and histopathological examinations). This was further confirmed by immunohistochemical staining where pretreatment with HMGlu (100 mg kg-1) markedly reduced NFκB, COX-2 and BAX positively-stained cells. Thus, it can be concluded that 7-hydroxy maltol-3-O-ß-d-glucoside can be a new pharmaceutically active agent with promising gastro-protective activity of natural origin.

Phytoconstituents from Polyscias guilfoylei leaves with histamine-release inhibition activity.

Phytochemical investigation of Polyscias guilfoylei leaves extract (PGE) led to the isolation of nine compounds, that is, ent-labda-8(17),13-diene-15,18-diol (1), stigmasterol (2), spinasterol (3), N-(1,3-dihydroxyoctadecan-2-yl) palmitamide (4), panaxydiol (5), 3-O-ß-d-glucopyranosylstigmasta-5,22-diene-3-ß-ol (6), (8Z)-2-(2 hydroxypentacosanoylamino) octadeca-8-ene-1,3,4-triol (7), 4-hydroxybenzoic acid (8), and tamarixetin 3,7-di-O-α-L-rhamnopyranoside (9). Compound 4 is reported in this study for the first time in nature whereas compound 9 is reported for the second time. Structural elucidation of the compounds was carried out using Nuclear Magnetic Resonance and Electrospray Ionization coupled with Mass Spectrometry spectroscopic analyses. PGE and compounds 4 and 9 exhibited weak cytotoxicity against both MCF-7 and HCT-116 cell lines using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay. The antimicrobial activity of PGE and compounds 4 and 9 was evaluated using the agar diffusion method. Escherichia coli was the most susceptible Gram-negative bacteria toward PGE with a minimum inhibitory concentration value of 9.76 µg/mL, whereas compounds 4 and 9 did not show any antimicrobial activity. Compound 4 exhibited promising inhibition of histamine release using U937 human monocytes with an IC50 value of 38.65 µg/mL.

Authentication and discrimination of green tea samples using UV-vis, FTIR and HPLC techniques coupled with chemometrics analysis.

Green tea is a popular beverage consumed worldwide. Its quality should be controlled adequately as the quality is influenced by several factors in addition to adulterations. This study aimed to develop a simple method for assessing the quality of green tea samples obtained from the South and the East Asian regions. The UV-vis, FTIR and HPLC data from 38 samples were subjected to multivariate analyses using the unsupervised recognition techniques comprising Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA). The model for their authentication was constructed and validated by applying the supervised recognition techniques as Soft Independent Modeling of Class Analogy (SIMCA) and Partial Least Square Discriminant Analysis (PLS-DA). The percentages of caffeine in the identified samples were determined using a validated HPLC assay in addition to in vitro determination of their antioxidant activity using DPPH radical-scavenging capacity assay. HCA and PCA based on UV data successfully distributed the tested samples into informative clusters. However, that obtained from visible data could only differentiate samples with respect to their powdered condition. On the contrary, PCA from FTIR and HPLC data could hardly discriminate any of the samples. The models constructed using SIMCA and PLS-DA showed a good class separation between the South and the East Asian samples. The percentages of caffeine in the identified samples and the IC50 in DPPH assay are greatly diverse among all the tested samples. Thus, UV spectroscopy and chemometrics have provided a simple and quick tool for the quality control of commercial green tea samples.

Syzygium aqueum: A Polyphenol- Rich Leaf Extract Exhibits Antioxidant, Hepatoprotective, Pain-Killing and Anti-inflammatory Activities in Animal Models.

Syzygium aqueum is widely used in folk medicine. A polyphenol-rich extract from its leaves demonstrated a plethora of substantial pharmacological properties. The extract showed solid antioxidant properties in vitro and protected human keratinocytes (HaCaT cells) against UVA damage. The extract also reduced the elevated levels of ALT, AST, total bilirubin (TB), total cholesterol (TC) and triglycerides (TG) in rats with acute CCl4 intoxication. In addition to reducing the high MDA level, the extract noticeably restored GSH and SOD to the normal control levels in liver tissue homogenates and counteracted the deleterious histopathologic changes in liver after CCl4 injection. Additionally, the extract exhibited promising anti-inflammatory activities in vitro where it inhibited LOX, COX-1, and COX-2 with a higher COX-2 selectivity than that of indomethacin and diclofenac and reduced the extent of lysis of erythrocytes upon incubation with hypotonic buffer solution. S. aqueum extract also markedly reduced leukocyte numbers with similar activities to diclofenac in rats challenged with carrageenan. Additionally, administration of the extract abolished writhes induced by acetic acid in mice and prolonged the response latency in hot plate test. Meanwhile, the identified polyphenolics from the extract showed a certain affinity for the active pockets of 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) explaining the observed anti-inflammatory activities. Finally, 87 secondary metabolites (mostly phenolics) were tentatively identified in the extract based on LC-MS/MS analyses. Syzygium aqueum displays good protection against oxidative stress, free radicals, and could be a good candidate for treating oxidative stress related diseases.

Evidence for the anti-inflammatory activity of Bupleurum marginatum (Apiaceae) extracts using in vitro and in vivo experiments supported by virtual screening.

OBJECTIVES: To explore the potential anti-inflammatory activity of Bupleurum marginatum extracts using in vitro and in vivo studies supported by virtual screening. METHODS: Antioxidant activity was assessed using the DPPH˙ and inhibition of 2-deoxyribose degradation assays. Anti-inflammatory activity was determined in vitro by measuring the suppression of prostaglandin E2 release (PGE2 ) in pancreatic cancer cells (MIA-PaCa-2) and the inhibition of 5-lipoxygenase whereas the rat paw oedema was used in vivo. The major constituents were docked in 5-lipoxygenase and cyclooxygenase-II active sites. KEY FINDINGS: Methanol and dichloromethane (DCM) extracts showed IC50 of 46.99 and 162.99 µg/ml in the DPPH˙, 1.52 and 2.12 µg/ml in inhibition of 2-deoxyribose degradation assays, respectively. They reduced PGE2 release by 41.33 and 52.85% at 25 µg/ml and inhibited 5-lipoxygenase with IC50 of 45.28 and 25.92 µg/ml, respectively. 50 and 70% reduction in the diameter of the carrageenan-induced rat paws with methanol and DCM extracts, respectively, with a marked decline in the inflammation score was observed. Rutin, a predominating compound, showed a strong interaction with the key amino acids in 5-LOX active site with interaction energy of -74.59 kcal/mol. CONCLUSIONS: Our study provides evidence for an interesting anti-inflammatory activity of B. marginatum aerial parts offering a natural anti-inflammatory agent.

High resolution UPLC-MS/MS profiling of polyphenolics in the methanol extract of Syzygium samarangense leaves and its hepatoprotective activity in rats with CCl4-induced hepatic damage.

Oxidative stress plays a crucial role in the development of several liver diseases. Many natural polyphenols can attenuate oxidative stress and liver injury. In this study, a phytochemical profiling of a methanol extract from leaves of Syzygium samarangense revealed 92 compounds belonging to flavonoids, phenolic acids, condensed tannins, and ellagitannins. The S. samarangense extract exhibited a noticeable antioxidant activity with an EC50 of 5.80 µg/mL measured by DPPH scavenging capacity assay, 2632 Trolox equivalents, 10 mM Fe2+ equivalents/mg of samples by TEAC and FRAP assays, respectively. The total phenolic content was 419 mg gallic acid equivalent GAE/g extract. In a cell-based model (HaCaT cells), the extract completely inhibited ROS production induced by UVA, and prevented GSH-depletion and p38 phosphorylation. In addition, the extract exhibited a substantial antioxidant and hepatoprotective activities in CCl4-treated rats, with an increase in GSH (reduced glutathione) and SOD (superoxide dismutase) activities by 84.75 and 26.27%, respectively, and a decrease of 19.08, 63.05, 52.21, 37.00, 13.26, and 15.15% in MDA, ALT, AST, TB (total bilirubin), TC (total cholesterol), and TG (total glycerides), respectively. These results were confirmed by histopathological analyses. We believe that Syzygium samarangense is a good candidate for further evaluation as an antioxidant and liver protecting drug.