Berberine alleviates chlorpyrifos-induced nephrotoxicity in rats via modulation of Nrf2/HO-1 axis.

Chlorpyrifos (CPS), an organophosphorus insecticide, is widely used for agricultural and non-agricultural purposes with hazardous health effects. Berberine (BBR) is a traditional Chinese medicine and a phytochemical with anti-inflammatory and anti-oxidative properties. The present study evaluated the effects of BBR against kidney damage induced by CPS and the underlying mechanisms. An initial study indicated that BBR 50 mg/kg was optimal under our experimental conditions. Then, 24 rats (6/group) were randomized into: control, BBR (50 mg/kg/day), CPS (10 mg/kg/day), and CPS + BBR. BBR was administration 1 h prior to CPS. Each treatment was delivered daily for a period of 28 consecutive days using a gastric gavage tube. Compared to CPS-alone treated rats, BBR effectively improved renal function by preventing the rise in serum urea, creatinine, and uric levels. The reno-protective effects of BBR were confirmed through a histological examination of kidney tissues. BBR restored oxidant-antioxidant balance in renal tissues mediated by Keap1/Nrf2/HO-1 axis modulation. In addition, BBR decreased nitric oxide (NO) and myeloperoxidase (MPO) activity. This was paralleled with the potent down-regulation of NF-κB. Furthermore, BBR exhibited anti-apoptotic activities supported by the upregulation of Bcl-2 and down-regulation of Bax and caspase-3 expression. In conclusion, our data suggest that BBR attenuates CPS-induced nephrotoxicity in rats by restoring oxidant-antioxidant balance and inhibiting inflammatory response and apoptosis in renal tissue. This is mediated, at least partly, by modulation of the Nrf2/HO-1 axis.

LC-MS based metabolic profiling and wound healing activity of a chitosan nanoparticle-loaded formula of Teucrium polium in diabetic rats.

Healing of wounds is the most deteriorating diabetic experience. Felty germander (Teucrium polium) possesses antioxidant, anti-inflammatory and antimicrobial activities that could accelerate wound healing. Further, nanohydrogels help quicken healing and are ideal biomaterials for drug delivery. In the current study, the chemical profiling, and standardization of T. polium methanolic extract by LC-ESI/TOF/MS/MS and quantitative HPLC-DAD analyses were achieved. The wound healing enhancement in diabetic rats by T. polium nanopreparation (TP-NP) as chitosan nanogel (CS-NG) and investigating the potential mechanisms were investigated. The prepared hydrogel-based TP-NP were characterized with respect to particle size, zeta potential, pH, viscosity, and release of major components. LC-ESI/TOF/MS/MS metabolomic profiling of T. polium revealed the richness of the plant with phenolic compounds, particularly flavonoids. In addition, several terpenoids were detected. Kaempferol content of T. polium was estimated to be 7.85 ± 0.022 mg/ g of dry extract. The wound healing activity of TP-NP was explored in streptozotocin-induced diabetic rats. Diabetic animals were subjected to surgical wounding (1 cm diameter). Then they were divided in 5 groups (10 each). These included Group 1 (untreated control rats), Group 2 received the vehicle of CS-NG; Group 3 (0.5 g of TP prepared in hydrogel), Group 4 (0.5 g of TP-NP), Group 5 represented a positive control treated with 0.5 g of a commercial product. All treatments were applied topically for 21 days. Application of TP-NP on skin wounds of diabetic animals accelerated the healing process as evidenced by epithelium regeneration, formation of granulation tissue followed by epidermal proliferation, along with keratinization as verified by H&E. This was confirmed through enhanced collagen synthesis, as shown by raised hydroxyproline content and Col1A1 gene expression. Moreover, TP-NP significantly alleviated wound oxidative burst and diminished the expressions of inflammatory biomarkers. Meanwhile, TP-NP could enhance the expressions of transforming growth factor beta1 (TGF-ß1), in addition to the angiogenic markers; vascular endothelia growth factor A (VEGFA) and platelet-derived growth factor receptor alpha (PDGFRα). Collectively, chitosan nanogel of T. polium accelerates wound healing in diabetic rats, which could be explained - at least partly - through alleviating oxidative stress and inflammation coupled with pro-angiogenic capabilities.

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics.

Since the emergence of the pandemic of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of antiviral phytoconstituents from medicinal plants against SARS-CoV-2 has been comprehensively researched. In this study, thirty-three plants belonging to seventeen different families used traditionally in Saudi Arabia were tested in vitro for their ability to inhibit the SARS-CoV-2 main protease (MPRO). Major constituents of the bio-active extracts were isolated and tested for their inhibition potential against this enzyme; in addition, their antiviral activity against the SARS-CoV-2 Egyptian strain was assessed. Further, the thermodynamic stability of the best active compounds was studied through focused comparative insights for the active metabolites regarding ligand-target binding characteristics at the molecular level. Additionally, the obtained computational findings provided useful directions for future drug optimization and development. The results revealed that Psiadia punctulata, Aframomum melegueta, and Nigella sativa extracts showed a high percentage of inhibition of 66.4, 58.7, and 31.5%, against SARS-CoV-2 MPRO, respectively. The major isolated constituents of these plants were identified as gardenins A and B (from P. punctulata), 6-gingerol and 6-paradol (from A. melegueta), and thymoquinone (from N. sativa). These compounds are the first to be tested invitro against SARS-CoV-2 MPRO. Among the isolated compounds, only thymoquinone (THY), gardenin A (GDA), 6-gingerol (GNG), and 6-paradol (PAD) inhibited the SARS-CoV-2 MPRO enzyme with inhibition percentages of 63.21, 73.80, 65.2, and 71.8%, respectively. In vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020 (accession number on GSAID: EPI_ISL_430820) revealed a strong-to-low antiviral activity of the isolated compounds. THY showed relatively high cytotoxicity and was anti-SARS-CoV-2, while PAD demonstrated a cytotoxic effect on the tested VERO cells with a selectivity index of CC50/IC50 = 1.33 and CC50/IC50 = 0.6, respectively. Moreover, GNG had moderate activity at non-cytotoxic concentrations in vitro with a selectivity index of CC50/IC50 = 101.3/43.45 = 2.3. Meanwhile, GDA showed weak activity with a selectivity index of CC50/IC50 = 246.5/83.77 = 2.9. The thermodynamic stability of top-active compounds revealed preferential stability and SARS-CoV-2 MPRO binding affinity for PAD through molecular-docking-coupled molecular dynamics simulation. The obtained results suggest the treating potential of these plants and/or their active metabolites for COVID-19. However, further in-vivo and clinical investigations are required to establish the potential preventive and treatment effectiveness of these plants and/or their bio-active compounds in COVID-19.

Zein-Stabilized Nanospheres as Nanocarriers for Boosting the Aphrodisiac Activity of Icariin: Response Surface Optimization and In Vivo Assessment.

Icariin (ICA), a main active compound of the Epimedium genus, is used as an aphrodisiac in traditional Chinese herbal medicine. Despite its therapeutic efficacy, ICA displays reduced oral absorption, and therefore, low bioavailability hindered its clinical application. Implementing nanotechnology in the field of formulation has been a focus to improve the efficacy of ICA. In this regard, polymeric nanoparticles find a potential application as drug delivery systems. A nanosphere formula was designed, aiming to improve the drug's efficacy. The proposed ICA nanosphere formula (tocozeinolate) was optimized using D-optimal response surface design. The concentrations of ICA (X1), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS, X2), zein (X3), and sodium deoxycholate (SDC, X4) expressed as percentages were investigated as quantitative independent variables. As per the experimental design, 23 formulations were developed, which were investigated for particle size (PS, nm), zeta potential (ZP, mV), and entrapment efficiency (EE, %) as response parameters. Numerical optimization and desirability approach were employed to predict the optimized variable levels that, upon combination, could result in minimized size and maximized zeta potential and ICA entrapment. The optimized ICA-tocozeinolate nanospheres showed a particle size of 224.45 nm, zeta potential of 0.961 mV, and drug entrapment of 65.29% that coincide well with the predicted values. The optimized ICA-tocozeinolate nanospheres were evaluated for sexual behavior in Wistar male rats compared to raw ICA at equivalent doses (20 mg/kg). In vivo assessment results showed significant sexual behavior enhancement by the optimized formulation, as evidenced by decreased average time of both mount latency (ML) and ejaculation latency (EL) to almost half those of raw ICA. Additionally, intromission latency (IL) time was reduced by 41% compared to the raw ICA. These results highlighted the potential of the proposed ICA-tocozeinolate nanospheres as a promising platform for improving the delivery and efficacy of therapeutic agents.

Wound Healing Activity of Opuntia ficus-indica Fixed Oil Formulated in a Self-Nanoemulsifying Formulation.

INTRODUCTION: Delayed wound healing represents a common health hazard. Traditional herbal products have been often utilized to promote wound contraction. The current study aimed at assessing the wound healing activity of Opuntia ficus-indica seed oil (OFI) and its self-nanoemulsifying drug delivery system (OFI-SNEDDS) formula in a rat model of full-thickness skin excision. METHODS: Based on droplet size, an optimized OFI-SNEDDS formula was prepared and used for subsequent evaluation. Wound healing activity of OFI and OFI-SNEDDS was studied in vivo. RESULTS: The optimized OFI-SNEDDS formula droplet size was 50.02 nm. The formula exhibited superior healing activities as compared to regular OFI seed oil-treated rats at day 14 of wounding. This effect was further confirmed by histopathological examinations of H&E and Masson's Trichrome-stained skin sections. Moreover, OFI-SNEDDS showed the highest antioxidant and anti-inflammatory activities as compared to OFI seed oil-treated animals. Both OFI and OFI-SNEDDS significantly enhanced hydroxyproline skin content and upregulated Col1A1 mRNA expression, accompanied by enhanced expression of transforming factor-beta (TGF-ß). Further, OFI-SNEDDS improved angiogenesis as evidenced by increased expression of vascular endothelial growth factor (VEGF). CONCLUSION: OFI possesses wound healing properties that are enhanced by self-emulsification of the oil into nano-droplets. The observed activity can be attributed, at least partly, to its anti-inflammatory, pro-collagen and angiogenic properties.

Euryops arabicus Promotes Healing of Excised Wounds in Rat Skin: Emphasis on Its Collagen-Enhancing, Antioxidant, and Anti-Inflammatory Activities.

Euryops arabicus Steud (E. arabicus) belongs to the family Asteraceae. It has several uses in folk medicine in the Arabian Peninsula. The current study aimed at evaluating the wound healing properties of the E. arabicus extract in rats. Primarily, E. arabicus successfully accelerated cell migration in vitro and it also showed no signs of dermal toxicity. Topical application of E. arabicus extract (5% or 20%) expedited healing of excised skin in rats. Histological examinations indicated that E. arabicus shortened epithelization period, stimulated fibroblast activity, and increased collagen deposition in wound tissues. The plant extract exerted antioxidant activity as evidenced by inhibition of GSH depletion and MDA accumulation and enhanced mRNA expression of Sod1 in wound tissues collected at the end of the experiment. Further, E. arabicus inhibited the rise of TNF-α and IL-1ß in the skin wound region. The anti-inflammatory was confirmed by the observed down regulation of Ptgs2, Nos2, IL-6, and NF-κB mRNA expression. In addition, the extract enhanced the expression of TGF-ß1 and HIF-1α in wounded skin tissues as indicated immunohistochemically. Conclusively, E. arabicus expedites excision wound healing in rats. Collagen-enhancing, anti-inflammatory, and antioxidant properties mediate the observed wound healing activity. These findings might contribute to our understanding of the ethnobotanical use of E. arabicus in wounds.

HPLC/MSn Profiling and Healing Activity of a Muco-Adhesive Formula of Salvadora persica against Acetic Acid-Induced Oral Ulcer in Rats.

Salvadora persica L. (S. persica, Siwak) is an ethnic plant that is widely used for improving oral hygiene. This study aimed to provide a phytochemical profiling of S. persica ethyl acetate fraction (SPEAF) and to evaluate the healing activity of a muco-adhesive formula of the fraction against acetic acid-induced oral ulcers in rats. HPLC-ESI-QTOF-MS-MS analysis of SPEAF resulted in the tentative identification of 56 metabolites containing fatty acids (23%), urea derivatives (10.5%) and sulphur compounds (10%), in addition to several amides, polyphenols and organic acids (6.5%, 5% and 2%, respectively). For the first time, 19 compounds were identified from S. persica. In vitro and in vivo experiments indicated that the extract is non-toxic. SPEAF exhibited superior healing activities compared to both the negative and positive control groups on days 7 and 14 of tongue ulcer induction. This was confirmed by histopathological examinations of haematoxylin and eosin-stained (H&E) and Masson's trichrome-stained tongue sections. Moreover, SPEAF showed potent anti-inflammatory activities, as evidenced by the inhibited expression of interleukin-6 (IL-6) and tumour necrosis alpha (TNF-α). Moreover, SPEAF exhibited potent antioxidant activity, as it prevented malondialdehyde (MDA) accumulation, reduced glutathione (GSH) depletion and superoxide dismutase (SOD) exhaustion. SPEAF significantly enhanced hydroxyproline tongue content and upregulated collagen type I alpha 1 (Col1A1) mRNA expression. SPEAF also improved angiogenesis, as shown by the increased mRNA expression of the angiopoietin-1 (Ang-1). In conclusion, S. persica has a wide range of secondary metabolites and ameliorates acetic acid-induced tongue ulcers in rats. This can be attributed, at least partly, to its anti-inflammatory, antioxidant, procollagen and angiogenic activities. These findings provide support and validity for the use of S. persica as a traditional and conventional treatment for oral disorders.

Osteoprotective Activity and Metabolite Fingerprint via UPLC/MS and GC/MS of Lepidium sativum in Ovariectomized Rats.

Lepidium sativum seeds are used traditionally to accelerate healing of bone fracture in addition to its culinary uses. This study aimed to characterize the osteoprotective effect of L. sativum in an ovariectomized rat model at two dose levels (50 and 100 mg/kg) using 17ß-estradiol as a positive reference standard. Moreover, a complete metabolite profile of L. sativum via UHPLC/PDA/ESI-MS, as well as headspace solid-phase microextraction (SPME)-GC/MS is presented. Results revealed that L. sativum extract exhibited significant anti-osteoporotic actions as evidenced by mitigating the decrease in relative bone weight concurrent with improved longitudinal and perpendicular femur compression strength. Further, the extract enhanced the serum bone formation biomarkers lactate dehydrogenase (LDH) activity and osteocalcin levels. The extract also inhibited exhaustion of superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) activities and accumulation of lipid peroxides in bone tissues. This is in addition to ameliorating the rise in the markers of bone resorption carboxyterminal telopeptide, type I (CTXI) and tartrate-resistant acid phosphatase (TRAP) and modulating receptor activator of nuclear factor kappa-Β ligand (RANKL)/ osteoprotegerin (OPG) expression. Metabolite characterization suggests that glucosinolates, lignans, coumarins, phenolic acids, and alkaloids mediate these anti-osteoporotic effects in a synergistic manner.

Euryops arabicus displays anti-inflammatory activities in experimental models.

ETHNOPHARMACOLOGICAL RELEVANCE: Euryops arabicus (Asteraceae) is grown in Arab Peninsula. Its aerial parts possess ethnomedicinal applications against several inflammatory conditions. AIM OF THE STUDY: To evaluate the anti-inflammatory activity of Euryops arabicus (E. arabicus) organic extract as well as its major polymethoxylated flavonoids. MATERIALS AND METHODS: Acute toxicity of the total extract of E. ararbicus was evaluated by assessing LD50. In vivo anti-inflammatory activity was evaluated in rats injected with carrageenan in the plantar area. Paw edema volume, histological changes and rats'stair climbing and motility were assessed. In vitro anti-inflammatory activity of the isolated compounds was evaluated in peripheral blood mononuclear cells (PBMCs) challenged with carrageenan. Inflammation markers were assessed in cellular lysates and collected media. RESULTS: The extract was found safe and considered unclassified with an oral LD50 > 2000 mg/kg in rats. Pretreatment of rats with a total extract of E. arabicus at doses of 100 and 250 mg/kg significantly inhibited carrageenan-induced increase in paw edema volume and histopathological changes. Also, it significantly ameliorated diminution of climbing and motility. Phytochemical studies led to the isolation and identification of five polymethoxylated flavonoids. The anti-inflammatory properties of the isolated compounds were evaluated in carrageenan-challenged peripheral blood mononuclear cells (PBMCs). All compounds exhibited appreciable antioxidant activities. Further, pre-incubation of the cells with the isolated metabolites significantly ameliorated the rise in cyclo-oxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1) induced by carrageenan challenge. Further, the compounds inhibited the leakage of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and myeloperoxidase (MPO) in media collected from stimulated cells. CONCLUSION: E. arabicus exhibited in vivo anti-inflammatory effects in the carrageenan model as it ameliorated rat paw edema, histopathological changes and movement dysfunction. in vitro activity of isolated compounds was confirmed in stimulated PBMCs. Thus, the anti-inflammatory activity of E. arabicus can be attributed, at least partly, to its anti-oxidant, anti-inflammatory and anti-chemotactic properties.

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.

The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginger (Zingiber officinale Roscoe) is a well known anti-inflammatory drug in the Egyptian, Indian and Chinese folk medicines, yet its mechanism of action is unclear. AIM OF THE STUDY: To explore its mechanism of action and to correlate it to its biophytochemicals. MATERIALS AND METHODS: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated using protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated using carrageenan-induced rat paw edema in rats at doses 25, 50, 100 and 200mg/kg b.wt. RESULTS: All the tested extracts showed significant (p< 0.1) in vitro anti-inflammatory activities. The strongest anti-lipoxygenase activity was observed for AE that was more significant than that of diclofenac (58% and 52%, respectively) at the same concentration (125µg/ml). Purification of AE led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G1, G2 and G8 exhibited potent activity in all the studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw edema in a dose-dependent manner. AE (at 200mg/kg) showed significant reduction in production of PGE2, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T-cell expressed and secreted (RANTES), myeloperoxidase (MPO) activity by 60%, 57%, 60%, 41%, 32% and 67%, respectively. AE at 100 and 200mg/kg was equipotent to indomethacin in reduction of NOx level and in increasing the total antioxidant capacity (TAC). Histopathological examination revealed very few inflammatory cells infiltration and edema after administration of AE (200mg/kg) prior to carrageenan. CONCLUSIONS: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. This was evidenced by the dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenishment the total antioxidant capacity.

Chrysin attenuates testosterone-induced benign prostate hyperplasia in rats.

Benign prostate hyperplasia (BPH) is a common age-related health problem affecting almost 3 out of 4 men in their sixties. Chrysin is a dietary phytoestrogen found naturally in bee propolis and various plant extracts. It possesses antioxidant, anti-inflammatory and anti-proliferative properties. The current study was conducted to explore the role chrysin plays in protection against testosterone-induced BPH in rats. On grounds of a preliminary experiment, a dose of chrysin (50 mg/kg) was chosen for further investigation. Testosterone significantly depleted glutathione, suppressed superoxide dismutase and catalase activities, and elevated lipid peroxidation. Moreover, it markedly scaled down the level of cleaved caspase-3 enzyme, reduced Bax/Bcl-2 ratio and mRNA expression of p53 and p21; conversely, protein expression of proliferating cell nuclear antigen was enhanced. Chrysin alleviated testosterone-induced oxidative stress and restored cleaved caspase-3 level, Bax/Bcl-2 ratio and mRNA expression of p53 and p21 to almost control levels. Chrysin prevented the increase in binding activity of nuclear factor kappa B (NF-κB) p65 subunit, mRNA expression of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 1 receptor (IGF-1R). These data highlight the protective role of chrysin against experimentally-induced BPH. This is attributed - at least partly - to its antioxidant, antiproliferative and proapoptotic properties.

Phenolics Isolated from Aframomum meleguta Enhance Proliferation and Ossification Markers in Bone Cells.

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane and diarylheptanoid groups were isolated from Aframomum meleguea seeds and identified as 6-gingerol (1), 6-paradol (2), 8-dehydrogingerdione (3), 8-gingerol (4), dihydro-6-paradol (5), dihydrogingerenone A (6), dihydrogingerenone C (7), 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyl diacetate (8), and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyl diacetate (9). The structures of isolated compounds were established by NMR and mass spectral data, in addition to referring to literature data. Exposure of MCF-7, MG-63, and SAOS-2 cells to subcytotoxic concentrations of the compounds under investigation resulted in accelerated proliferation. Among them, paradol was selected for further detailed biochemical analysis in SAOS-2 cells. DNA flowcytometric analysis of cell cycle distribution revealed that paradol did not induce any significant change in the proliferation index of SAOS-2 cells. Assessment of osteogenic gene expression revealed that paradol enhanced the expression of osteocyte and osteoblast-related genes and inhibited osteoclast and RUNX suppressor genes. Biochemically, paradol enhanced alkaline phosphatase activity and vitamin D content and decreased the osteoporotic marker acid phosphatase. In conclusion, paradol, which is a major constituents of A. melegueta seeds, exhibited potent proliferative and ossification characteristics in bone cells.

Polyphenols from Erythrina crista-galli: Structures, Molecular Docking and Phytoestrogenic Activity.

OBJECTIVES: The current study aimed at exploring the secondary metabolites content of Erythrina crista-galli aqueous methanol extract and assessing its phytoestrogenic and cytoprotective activities. METHODS: Isolation of the compounds was carried out using conventional chromatographic techniques. The structures of the isolated compounds were elucidated based on the UV, NMR spectral data along with their mass-spectrometric analyses. The phytoestrogenic activity was evaluated in-silico and in vitro using the Arabidopsis thaliana pER8: GUS reporter assay and the proliferation-enhancing activity of MCF-7 cells. KEY FINDINGS: Phytochemical investigation of E. crista-galli aqueous methanol extract resulted in the isolation and identification of five flavonoids. The plant extract and its fractions showed significant estrogenic activities compared to controls. CONCLUSION: Five flavonoids were identified from E. crista-galli aqueous methanol extract. To the best of our knowledge, among these flavonoids, apigenin-7-O-rhamnosyl-6-C-glucoside was isolated for the first time from nature. Moreover, luteolin-6-C-glucoside was isolated for the first time from this plant. The plant revealed promising phytoestrogenic activities. This gives rationale to some of its pharmacological properties and suggests additional phytoestrogenic effects, which have not been reported yet.

Genistein improves sensorimotor gating: Mechanisms related to its neuroprotective effects on the striatum.

Huntington's disease (HD) is a neurodegenerative disorder, characterized by selective atrophy in the striatum, particularly the medium spiny GABAergic efferent neurons. This results in striatal sensorimotor gating deficits. Systemic administration of 3-nitropropionic acid (3-NPA) produces selective lesions mimicking those of HD. Males were found to be more susceptible to 3-NPA-induced neurotoxicity than females, suggesting neuroprotective effects of estrogens. Phytoestrogens, including genistein, are good estrogenic alternatives that keep their beneficial effects on non-reproductive organs and lack the potential hazardous side effects. The current study was designed to investigate the potential beneficial effects of genistein in 3-NPA-induced HD in ovariectomized rats. Results showed that 3-NPA (20 mg/kg) administration caused significant disruption of the rats' locomotor activity and prepulse inhibition. In addition, it decreased striatal ATP levels and increased oxidative stress, inflammatory and apoptotic markers with striatal focal hemorrhage and gliosis. Pretreatment with 17ß-estradiol (2.5 mg/kg) or genistein (20 mg/kg) led to a significant improvement of behavioral parameters, increased ATP production, decreased oxidative stress, attenuated inflammation and apoptosis. Therefore, this study suggests potential neuroprotective effects of genistein in ovariectomized rats challenged with 3-NPA.

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

Mechanistic Evidence of Viscum schimperi (Viscaceae) Antihyperglycemic Activity: From a Bioactivity-guided Approach to Comprehensive Metabolite Profiling.

Diabetes mellitus is possibly the world's largest growing metabolic disorder. Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Viscum schimperi Engl. is a plant growing in Saudi Arabia and known for its antidiabetic activity. The potential antidiabetic activity of its methanol extract as well as its chloroform, n-butanol, and the remaining water fractions was evaluated in streptozotocin-induced diabetic rats at two dose levels. The antidiabetic activity was assessed through the determination of fasting blood glucose level, insulin levels, area under the curve (AUC) in oral glucose tolerance test, glucose absorption in isolated rat gut assay, and glucose uptake by psoas muscle. Moreover, large-scale untargeted metabolite profiling of methanol extract was performed via UPLC-PDA and qTOF-MS (ultra-performance liquid chromatography photodiode array detection and quadrupole time-of-flight mass spectrometry) respectively, to explore its chemical composition and standardization of its extract. Multivariate statistical analysis including principal component analysis and orthogonal projection to latent structures discriminant analysis was used to determine bioactives in its fractions. In conclusion, oleanane triterpenes and O-caffeoyl quinic acid conjugates were the major compounds that might account for antihyperglycemic effect of the plant.

The effect of pomegranate fruit extract on testosterone-induced BPH in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in the pathology of BPH. Pomegranate contains a variety of polyphenolic compounds that have been studied in a medley of diseases for their anti-oxidant, anti-inflammatory and pro-apoptotic properties. Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on the development of BPH using a testosterone-induced BPH model in rats. METHODS: A total of 48 rats were randomly divided into six groups of eight, one group served as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four groups, three of them received PFE by oral gavage daily at doses of 25, 50, and 100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg without induction of BPH. RESULTS: PFE at a dose of 100 mg/kg was the most effective in decreasing testosterone-induced increase in prostate weight, prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68% respectively and in preventing the accompanying histological changes. In the BPH model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and 0.88 of the control group values respectively, and significantly increased MDA by >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values respectively, whereas MDA was significantly decreased by 72% compared with the testosterone treated group. In addition to this, at the range of doses studied, PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index. CONCLUSION: The current findings elucidate the effectiveness of PFE in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its anti-oxidant, anti-inflammatory, and pro-apoptotic properties.

Anti-inflammatory activity of selected plants from Saudi Arabia.

Thirteen selected Saudi Arabian plants, belonging to seven different families, were tested for possible anti-inflammatory activity using the carrageenin-induced paw edema model in rats. The methanolic extracts of Vernonia schimperi, Trichodesma trichodesmoides var. tomentosum, and Anabasis articulata exhibited the highest anti-inflammatory activity. The active extracts were further subjected to fractionation with chloroform, ethyl acetate, and n-butanol and tested together with their mother liquor for their anti-inflammatory activity in the same rat model. The most potent fractions were the n-butanol fractions of Anabasis articulata and Vernonia shimperi and the aqueous mother liquor of Trichodesma trichodesmoides. Nevertheless, the three potent methanolic extracts showed higher anti-inflammatory activities than their individual fractions. The antioxidant properties were assessed by their in vitro 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activities. It was concluded that the anti-inflammatory activity is dependent, at least in part, on the reduction of prostaglandin (PGE2) and tumour necrosis factor-alpha (TNF-alpha) levels and cyclooxygenase-2 (COX-2) activity.

Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects.

Caffeic acid phenethyl ester (CAPE) is an important active component of honey bee propolis that possesses a plethora of biological activities. Propolis is used safely in traditional medicine as a dietary supplement for its therapeutic benefits. This review highlights the recently published data about CAPE bioavailability, anti-inflammatory, neuroprotective; hepatoprotective and cardioprotective activities. CAPE showed promising efficacy both in vitro and in vivo studies in animal models with minimum adverse effects. Its effectiveness was demonstrated in multiple target organs. Despite this fact, it has not been yet investigated as a protective agent or a potential therapy in humans. Investigation of CAPE efficacy in clinical trials is strongly encouraged to elucidate its therapeutic benefit for different human diseases after performing full preclinical toxicological studies and gaining more insights into its pharmacokinetics.