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Erythrina bidwillii Lindl., Leguminosae, constitutes a valuable crop for horticulture and medicine; however, it is rarely investigated. Menopause is a crucial transitional period in women's health. Women worldwide consider the use of phytoestrogens as a safe hormone replacement therapy to alleviate detrimental menopausal symptoms. Thus, the discovery of novel phytoestrogens is highly demanded. The present study aimed to investigate, for the first time, the metabolomic profile and the estrogenic potential of E. bidwillii Lindl. leaf. Ultra‐performance liquid chromatography–electrospray ionization‐tandem mass spectrometry and gas chromatography–mass spectrometry metabolite profiling revealed the prevalence of alkaloids, flavonoids, isoflavonoids and fatty acids. Additionally, five erythrinan alkaloids, cristanine A (1), 8‐oxoerythraline (2), (+)‐erythrinine (3), (+)‐erythraline (4) and 8‐oxoerythrinine (5), along with the isoflavonoid genistin (6), were isolated. Erythrina bidwillii leaf extract exhibited significant in vivo estrogenic, anti‐osteoporotic, anti‐hyperlipidemic, hepatoprotective, and nephroprotective activities, utilizing ovariectomized rat model. Moreover, ethyl acetate and hexane fractions possessed significant in vitro estrogeic potential on MCF‐7 cell lines. An in silico study of the isolated metabolites revealed that (+)‐erythrinine (3) and 8‐oxoerythrinine (5) exhibited the highest affinity for ERα and ERβ, respectively, modeling them as potential estrogenic lead metabolites. Therefore, E. bidwillii leaf could be employed as promising hormone replacement therapy for postmenopausal women after thorough clinical trials. [ABSTRACT FROM AUTHOR]

Panicum antidotale has traditionally been used as a poultice to alleviate local inflammation and painful diseases. This study aimed to evaluate the antiinflammatory, 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 β protein indicated their potential interaction within the active sites of both enzymes. Thus, P. antidotale serves as an effective natural woundhealing, anti-inflammatory, analgesic, and antipyretic agent. [ABSTRACT FROM AUTHOR]

This study aimed to assess the potential of Lactuca serriola (Asteraceae) seed n-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were evaluated for the anxiolytic potential using the hole-board, the elevated plus maze and the light/dark test. A phenobarbitone-induced sleep test was employed for the evaluation of sedative potential. Acute anticonvulsant activity was evaluated by picrotoxin and strychnine-induced convulsion models. All extracts significantly reduced the number of head dips where n-hexane extract (400 mg/kg) showed 96.34% reduction in the tendency of head dipping when compared with the control. Mice treated with extracts preferred elevated plus maze open arms and were shown to lack open arms evasion, especially n-hexane extract (400 mg/kg)—which showed 456.14%—increased the duration of open arm stay with the respective control group. By reducing sleep latency and greatly lengthening sleep duration, L. serriola enhanced the effects of barbiturate-induced sleep. A significant increase in convulsion latency and decrease in convulsions induced by picrotoxin and strychnine duration was observed in all extract-treated groups. All the extracts exhibited anti-epileptogenic potential as the seizure score in pentylenetetrazol (PTZ)-induced kindling in mice was reduced significantly. Maximum protection was afforded by chloroform extract that reduced the seizure score by 79.93% compared with the PTZ group. Chloroform executed antioxidant effect by elevating super oxide dismutase (SOD) by 126%, catalase (CAT) by 83.53%, total glutathione (tGSH) by 149%, and reducing malondialdhyde (MDA) levels by 36.49% in the brain tissues that is further consolidated by histopathological examination. Metabolic profiling of the most active chloroform extract using Gas chromatography coupled with mass showed the presence of 16 compounds. This anti-epileptic activity was further confirmed via in silico molecular modelling studies in the active site Gamma-aminobutyric acid aminotransferase (GABA-AT) where all of the tested metabolites illustrated a potent inhibitory potential towards GABA-AT with hexadecanoic acid, 15-methyl-, methyl ester followed by octadecanoic acid, methyl ester showed the best fitting. The results indicated the possible anxiolytic and anti-epileptogenic potential of the plant and further consolidated the ethnopharmacological use of L. serriola seeds. [ABSTRACT FROM AUTHOR]

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50 equal to 8.68 μg/mL but with moderate activity in galvinoxyl assay with IC50 of 21.82 μg/mL and mild activity in the β-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC50 = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 28.69 and 4.93 μg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 μg GAE/mg) and flavonoids (24.30 ± 0.44 μg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research. [ABSTRACT FROM AUTHOR]

In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with PRD_002214, the co-crystallized ligand of Mpro (PDB ID: 6LU7), and favored thirty compounds. Subsequently, the fingerprint study performed with respect to PRD_002214 resulted in the election of sixteen compounds (7, 128, 130, 156, 157, 158, 180, 184, 203, 204, 210, 237, 264, 276, 277, and 278). Then, results of molecular docking versus Mpro PDB ID: 6LU7 favored eight compounds (128, 130, 156, 180, 184, 203, 204, and 278) based on their binding affinities. Then, in silico toxicity studies were performed for the promising compounds and revealed that all of them have good toxicity profiles. Finally, molecular dynamic (MD) simulation experiments were carried out for compounds 130, 184, and 278, which exhibited the best binding modes against Mpro. MD tests revealed that luteoside C (130) has the greatest potential to inhibit SARS-CoV-2 main protease. [ABSTRACT FROM AUTHOR]

The anti-osteoporotic activity of ethanol extract from the Matricaria chamomilla L. flower was evaluated using steroid-induced osteoporosis in a rat model for the first time. Biochemical parameters such as serum calcium, phosphate, magnesium, creatinine, and alkaline phosphatase were assessed. At a 400 mg/kg body weight dose, the extract showed 54.01% and 27.73% reduction in serum calcium and phosphate ions serum levels, respectively. Meanwhile, it showed a 20% elevation in serum magnesium level, compared to the steroid-treated group. It also showed a significant decrease in creatinine and alkaline phosphatase levels, by 29.41% and 27.83%, respectively. The obtained results were further supported by biomechanical analyses, which revealed that a 400 mg/kg body weight dose of the flower extract increased bone strength and thickness. At the same time, it does not affect the bone length, compared to the diseased group. Histopathological examination revealed that the extract showed a significant increase in trabecular thickness, and it had restored the architecture of the cortical and trabecular structure with well-organized bone matrix. The possible inhibitory effect of the major phenolic compounds identified from the plant extract on cathepsin K was investigated using molecular docking. Rutin (4) had the best-fitting score within the active site, as evidenced by the free binding energy, (∆G = −54.19 Kcal/mol). ADMET/TOPKAT revealed that the examined compounds had variable pharmacodynamics and pharmacokinetic properties that could be improved to enhance the bioavailability during incorporation in various dosage forms. Thus, it can be concluded that this plant extract showed potential therapeutic benefits for osteoporosis. [ABSTRACT FROM AUTHOR]

Lobularia libyca (L. libyca) is a traditional plant that is popular for its richness in phenolic compounds and flavonoids. The aim of this study was to comprehensively investigate the phytochemical profile by liquid chromatography, electrospray ionization and tandem mass spectrometry (LC-ESI-MS), the mineral contents and the biological properties of L. libyca methanol extract. L. libyca contains significant amounts of phenolic compounds and flavonoids. Thirteen compounds classified as flavonoids were identified. L. libyca is rich in nutrients such as Na, Fe and Ca. Moreover, the methanol extract of L. libyca showed significant antioxidant activity without cytotoxic activity on HCT116 cells (human colon cancer cell line) and HepG2 cells (human hepatoma), showing an inhibition zone of 13 mm in diameter. In silico studies showed that decanoic acid ethyl ester exhibited the best fit in β-lactamase and DNA gyrase active sites; meanwhile, oleic acid showed the best fit in reductase binding sites. Thus, it can be concluded that L. libyca can serve as a beneficial nutraceutical agent, owing to its significant antioxidant and antibacterial potential and due to its richness in iron, calcium and potassium, which are essential for maintaining a healthy lifestyle. [ABSTRACT FROM AUTHOR]

Phytochemical characterization of the ethyl acetate fraction of Saussurea hypoleuca root extract resulted in the isolation of oleic acid (1) and luteolin (2), which were isolated for the first time from Saussurea hypoleuca root. A heavy metal analysis of the root powder performed using atomic absorption spectroscopy showed that the contents of iron, cadmium, lead, zinc, nickel, and copper were within the certified limits according to the WHO guidelines. Differential scanning calorimetry (DSC) revealed its crystalline and amorphous nature; meanwhile, standardization of the root with UHPLC revealed the presence of 14.79 ± 0.015 µg/mL of luteolin. Both the total methanol extract and the ethyl acetate fraction of the plant root held significant anthelmintic activity. Oleic acid and luteolin exhibited potent antioxidant activity, evidenced by their IC50 values, which were equal to 47.0 and 119.8 µg/mL, respectively, in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. In silico studies showed that luteolin exerted the highest fitting within the binding sites of NADPH oxidase (Nox). For myeloperoxidase (MP), oleic acid revealed the best fitting in its active sites. The results of ADMET (absorption, distribution, metabolism, excretion, and toxicity) and TOPKAT (toxicity prediction) protocols revealed acceptable pharmacodynamic and pharmacokinetic characteristics, in addition to reasonable toxicity characteristics for both compounds. Thus, they can be incorporated into pharmaceutical dosage forms to combat oxidative stress. [ABSTRACT FROM AUTHOR]

Ecdysteroids represent arthropods' steroidal hormones, and they exist in about 5–6% of plant species. In this study, the enzyme inhibitory activity of 20 ecdysteroids was assessed for the first time via determining their inhibition versus acetylcholinesterase, butyrylcholinesterase, tyrosinase, as well as α-amylase enzymes. Furthermore, 20-Hydroxyecdysone-2,3,22-tri-O-acetate (4) showed the highest inhibition of acetylcholinesterase and butyrylcholinesterase with values of 5.56 and 4.76 mg GALAE/g, respectively. All ecdysteroids displayed tyrosinase inhibitory effects, whereas the most potent was viticosterone E (7) with 78.88 mg KAE/g. Most ecdysteroids had similar amylase inhibitory properties; meanwhile, the best α-amylase inhibitory potential was observed with viticosterone E-diacetonide (18) (0.35 mmol ACAE/g). Most of the tested compounds showed tyrosinase inhibitory potential; therefore, they were exposed to molecular docking evaluation using the tyrosinase enzyme. Viticosterone E (7) showed the best ranking score with a docking score of −5.716 Kcal/mol and made three separate H-bonds with Gly281, Asn81, and His85. From ADMET /TOPKAT in silico evaluation, it was obvious that most of the compounds displayed reasonable pharmacodynamic and pharmacokinetic properties; however, their toxicity should be carefully monitored by adjusting their doses while investigating their activity after incorporation into dosage forms. Principal component analysis (PCA) based upon the in vitro and in silico data was carried out to visualize the differences between the tested compounds better. PCA score plot successfully classifies the compounds into four main clusters that, in turn, reflects the similarities and differences among the clustered compounds with respect to their biological, pharmacokinetic, and pharmacodynamic properties that are mainly influenced by the similarity in the chemical structure. Thus, ecdysteroids can act as effective drug entities for alleviating several disorders owing to their enzyme inhibitory potential. [ABSTRACT FROM AUTHOR]

The essential oils of Jatropha intigrimma, J. roseae and J. gossypifolia (Euphorbiaceae) were analyzed employing GC/MS (Gas Chromatography coupled with Mass Spectrometry) analyses. A total of 95 volatile constituents were identified from J. intigrimma, J. gossypifolia and J. roseae essential oils, accounting for 91.61, 90.12, and 86.24%, respectively. Chemometric analysis using principal component analysis (PCA) based on the obtained GC data revealed the formation of three discriminant clusters due to the placement of the three Jatropha species in three different quadrants, highlighting the dissimilarity between them. Heneicosane, phytol, nonacosane, silphiperfol-6-ene, copaborneol, hexatriacontane, octadecamethyl-cyclononasiloxane, 9,12,15-Octadecatrienoic acid, methyl ester and methyl linoleate constitute the key markers for their differentiation. In vitro antibacterial activities of the essential oils were investigated at doses of 10 mg/mL against the Gram-negative anaerobe Escherichia coli using the agar well diffusion method and broth microdilution test. J. gossypifolia essential oil showed the most potent antimicrobial activity, demonstrating the largest inhibition zone (11.90 mm) and the least minimum inhibitory concentration (2.50 mg/mL), followed by the essential oil of J. intigrimma. The essential oils were evaluated for their anti-adhesion properties against the Gram-negative E. coli biofilm using a modified method of biofilm inhibition spectrophotometric assay. J. intigrimma essential oil showed the most potent biofilm inhibitory activity, demonstrating the least minimum biofilm inhibitory concentration (MBIC) of 31.25 µg/mL. In silico molecular docking performed within the active center of E. coli adhesion protein FimH showed that heneicosane, followed by cubebol and methyl linoleate, displayed the best fitting score. Thus, it can be concluded that the essential oils of J. gossypifolia and J. intigrimma leaves represent promising sources for antibacterial drugs with antibiofilm potential. [ABSTRACT FROM AUTHOR]

Cannabis sativa L. is an annual herbaceous plant that belongs to the family Cannabinaceae. In this study, the potential use of forty-five cannabinoids, previously identified from Cannabis sativa to alleviate COVID-19 infection via prohibition of crucial SARS-CoV-2 proteins using molecular docking, was examined. In silico studies were performed on three vital enzymes that serve as principle therapeutic targets to prevent SARS-CoV-2 replication. These enzymes are the main protease SARS-CoV-2 MPro, papain-like protease SARS-CoV-2 PLpro and angiotensin-converting enzyme 2 (ACE2). Regarding SARS-CoV-2 MPro, cannabichromanon (32) showed the best fitting within its active centers, followed by cannabinolic acid (22) and cannabinol (21), displaying ∆G of −33.63, −23.24, and −21.60 kcal/mol, respectively. Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with ∆G values of −28.36, −22.81, and −19.89 kcal/mol. Furthermore, cannabichromanon (32), cannabinolic acid (22), and cannabinol (21) showed considerable fitting within the active sites of angiotensin-converting enzyme 2 (ACE2) evidenced by their significant ∆G values that were estimated as −41.77, −31.34, and −30.36 kcal/mol, respectively. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) evaluation was performed on the tested cannabinoids to further explore their pharmacokinetics, pharmacodynamics, and toxicity properties. The results indicated the considerable pharmacokinetic, pharmacodynamic, and toxicity properties of cannabinol (21), cannabinolic acid (22), cannabichromanon (32), and cannabicyclolic acid (41) that showed best fitting scores within the active sites of the tested enzymes. Multivariate data analysis revealed that cannabichromanon and cannabinolic acid showed a discriminant nature and hence can be incorporated in pharmaceutical dosage forms to alleviate COVID-19 infection. [ABSTRACT FROM AUTHOR]

Background: The Australian plant Eremophila maculata F. Muell (Scrophulariaceae) is cultivated worldwide as an ornamental plant.Purpose: This study was designed to assess the antioxidant and hepatoprotective activities of a methanol extract from E. maculata leaves (EMM) both in vitro and in vivo (rats) experiments. Detailed phytochemical study was done on the extract followed by molecular docking experiments on TNF-α ascertain the efficacy of the isolated compounds.Methods: The antiproliferative activity was evaluated in the human cancer cell lines A-495, PC3 and HepG2 cells using the SRB method. The antioxidant activitywas evaluated in vitro using the DPPH• assay while the hepatoprotective properties were investigated by determining the amelioration of CCl4-induced cytotoxicity and oxidative stress in HepG2 cells. The activity was confirmed in vivo by studying tamoxifen-induced hepatotoxicity in rats. An in-depth phytochemical investigation of a methanol extract was performed using 1D and 2D NMR experiments. In silico molecular modeling studies of the isolated compounds on TNF-α (PDB ID 2AZ5) were carried out using Discovery Studio 2.5 software applying C-Docker protocol.Results: The IC50 values of EMM were >500µg/ml for both PC3 and HepG2 cells indicating its safety. Similar to the standard drug silymarin, EMM could restore AST, ALT values; replenish GSH level, SOD activity and TAC in vitro. The hepatoprotective activity was confirmed in vivo in which the extract (20mg/kg body weight) decreased ALT and AST levels by 45.23 and 45.79%, respectively as compared to the tamoxifen treated groups. Oxidative stress was reduced by lowering of thiobarbituric acid reactive substances by 28.57%. Additionally, hepatocyte inflammation was improved by reducing the pro-inflammatory mediator TNF-α by 54.29%. Phytochemical investigation resulted in the isolation of a rare naturally-occurring lignan glycoside, namely pinoresinol-4-O-[6″-O-(E)-feruloyl]-β-D-glucopyranoside for the first time from the Scrophulariaceae in addition to 12 known compounds.Pinoresinol-4-O-[6''-O-(E)-feruloyl]-β-D-glucopyranoside was the strongest inhibitor of TNF-α as evidenced from its higher fitting scores comparable to lead compound.Conclusions: These findings highlighted for the first time that EMM could be an interesting candidate as a safe, natural liver supplement for relieving of various hepatic disorders and counteracting the effect of many xenobiotics. [ABSTRACT FROM AUTHOR]

Buddleia indica Lam. is an ornamental evergreen shrub with few reports concerning its phytoconstituents and biological activities. Herein, the antihyperglycaemic activity of B. indica leaves methanol extract (BIT) was evaluated for the first time using in vitro and in vivo studies. Molecular modelling was performed for its major phytoconstituents that were further subjected to ADME/TOPAKT (absorption, distribution, metabolism, excretion and toxicity) prediction. BIT revealed considerable reduction in glucose concentration by 9.93% at 50 μg/mL using 3T3-L1 adipocyte culture. It displayed substantial inhibition versus α-glucosidase and α-amylase with IC50 205.2 and 385.06 μg/mL, respectively. In vivo antihyperglycaemic activity of BIT and the ethyl acetate fraction (BIE) was performed using streptozotocin-induced diabetes in rat model. BIT and BIE effectively ameliorate oxidative stress markers in addition to reducing serum blood glucose by 56.08 and 54.00%, respectively, and are associated with a substantial increase in serum insulin by 4.1 and 12.7%, respectively. This can be attributed to its richness with polyphenolic compounds comprising flavonoids, phenolic acids, phenyl propanoids and iridoids. Molecular docking showed that verbascoside and kaempferol displayed the highest fitting within human α-amylase (HA) and human α-glucosidase (HG) active sites, respectively. They showed reasonable pharmacokinetic, pharmacodynamic and toxicity properties, as revealed by ADME/TOPKAT study. [ABSTRACT FROM AUTHOR]

In-depth botanical characterization was performed on Premna odorata Blanco (Lamiaceae) different organs for the first time. The leaves are opposite, hairy and green in color. Flowers possess fragrant aromatic odors and exist in inflorescences of 4–15 cm long corymbose cyme-type. In-depth morphological and anatomical characterization revealed the great resemblance to plants of the genus Premna and of the family Lamiaceae, such as the presence of glandular peltate trichomes and diacytic stomata. Additionally, most examined organs are characterized by non-glandular multicellular covering trichomes, acicular, and rhombic calcium oxalate crystals. P. odorata leaves n-hexane fraction revealed substantial anti-tuberculous potential versus Mycobacterium tuberculosis, showing a minimum inhibition concentration (MIC) of 100 μg/mL. Metabolic profiling of the n-hexane fraction using gas-chromatography coupled to mass spectrometry (GC/MS) analysis revealed 10 major compounds accounting for 93.01%, with trans-phytol constituting the major compound (24.06%). The virtual screening revealed that trans-phytol highly inhibited MTB C171Q receptor as M. tuberculosis KasA (β-ketoacyl synthases) with a high fitting score (∆G = −15.57 kcal/mol) approaching that of isoniazid and exceeding that of thiolactomycin, the co-crystallized ligand. Absorption, distribution, metabolism, excretion and toxicity predictions (ADME/TOPKAT) revealed that trans-phytol shows lower solubility and absorption levels when compared to thiolactomycin and isoniazid. Still, it is safer, causing no mutagenic or carcinogenic effects with higher lethal dose, which causes the death of 50% (LD50). Thus, it can be concluded that P. odorata can act as a source of lead entities to treat tuberculosis. [ABSTRACT FROM AUTHOR]

Fermentation of the marine-derived fungus Aspergillus falconensis , isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3 – 8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH 4) 2 SO 4 that resulted in the accumulation of three further known compounds (9 – 11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted for all isolated compounds on crucial enzymes involved in the formation, progression and metastasis of cancer which included human cyclin-dependent kinase 2 (CDK-2), human DNA topoisomerase II (TOP-2) and matrix metalloproteinase 13 (MMP-13). Diorcinol (7), sulochrin (9) and monochlorosulochrin (10) displayed notable stability within the active pocket of CDK-2 with free binding energy (ΔG) equals to −25.72, −25.03 and −25.37 Kcal/mol, respectively whereas sulochrin (9) exerted the highest fitting score within MMP-13 active center (ΔG = −33.83 Kcal/mol). In vitro cytotoxic assessment using MTT assay showed that sulochrin (9) exhibited cytotoxic activity versus L5178Y mouse lymphoma cells with an IC 50 value of 5.1 µM and inhibition of migration of MDA-MB 231 breast cancer cells at a concentration of 70 µM. [ABSTRACT FROM AUTHOR]

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. This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM). 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). 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-κβ 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. Thus , Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals. [Display omitted] • Opuntia monacantha was traditionally used to treat pain and inflammation. • Its showed promising anti-inflammatory and anti-arthritis activity in different in vivo models • HPLC previously showed that phenolic acids and flavonoids existed in the ethanol extract. • Molecular docking displayed pronounced inhibitory potential versus glutaminase 1 (GLS1) [ABSTRACT FROM AUTHOR]