Novel antiarthritic mechanisms of Azelaic acid against CFA-induced arthritis in rats by modulating pro- and anti-inflammatory cytokines network.

An immunologic system attacking the body's own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential biologic functions, including the regulation of the immune system, inflammation, cell division, and tissue repair, are carried out by cytokines. Natural compounds are an effective treatment for autoimmune illnesses by modulation of inflammatory cytokines and infiltration of leukocytes into the inflamed tissue. Here, anti-arthritic study was carried out using oral administration of Azelaic acid (AzA) for 28 days with doses (20, 40, and 80 mg/kg) in Complete Freund's Adjuvant (CFA) induced arthritis model. AzA ameliorated the adjuvant-induced arthritis by decreasing arthritic score, paw volume, improved body-weight alterations and serum levels of PGE2, 5-LOX and anti-ccp. AzA showed significant down regulation of NF-κB, COX-II, TNF-α, IL-17, IL-1ß, IL-6, and up regulation of IL4 and IL10. Hemoglobin and RBCs count remarkably increased and ESR, CRP, platelets, WBCs levels markedly reduced in post treatment. In addition, the weakened SOD (superoxide dismutase), Catalase (CAT), Glutathione (GSH) activity and the increased levels of malondialdehyde (MDA) were all reversed by AzA treatment. And showed improved radiographical and histologic alterations in the structure of the joints. Molecular docking studies targeting COX-II, iNOS, TNF-α, 5-LOX, IL4, IL10, IL-6, and IL-17 establish a correlation between theoretical and experimental results. Results showed that AzA inhibit pro-inflammatory cytokines (COX-II, TNF-α, 5-LOX, IL-17, NF-κB, IL-1ß, and IL-6) and increase anti-inflammatory cytokines, which supported the anti-arthritic and immunomodulatory potential of AzA.

Molecular insights of Eucalyptol (1,8-Cineole) as an anti-arthritic agent: in vivo and in silico analysis of IL-17, IL-10, NF-κB, 5-LOX and COX-2.

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real-time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1ß and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1ß. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity.

Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150 mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.

Role of medicinal herbs and phytochemicals in post burn management.

Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing involves initiation of inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Despite the availability of multiple preparations for management of burn wound, there is dire need for efficacious alternative agents. Current approaches for burn wound management include pharmaceutical agents and antibiotics. However, high cost of synthetic drugs and accelerated resistance to antibiotics is challenging for both developed and developing nations. Among alternative options, medicinal plants have been a biocompatible, safe and affordable source of preventive/curative approaches. Due to cultural acceptance and patient compliance, there has been a focus on the use of botanical drugs and phytochemicals for burn wound healing. Keeping in consideration of medicinal herbs and phytochemicals as suitable therapeutic/adjuvant agents for burn wound management, this review highlights therapeutic potential of 35 medicinal herbs and 10 phytochemicals. Among these, Elaeis guineensis, Ephedra ciliate and Terminalia avicennioides showed better burn wound healing potential with varied mechanisms such as modulation of TNF-alpha, inflammatory cytokines, nitric oxide, eicosanoids, ROS and leukocyte response. Phytochemicals (oleanolic acid, ursolic acid, kirenol) also showed promising role in burn wound management though various pathways involving such as down regulation of TNF-alpha, IL-6 and inflammatory mediators including plasma proteases and arachidonic acid metabolites. This review provides a pavement for therapeutic/adjuvant use of potential botanical drugs and novel druggable phyto-compounds to target skin burn injury with diverse mechanisms, affordability and safety profile.

Antidiabetic activity of Berberis brandisiana is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats.

Medicinal plants play a key role in protection of chronic non-communicable ailments like diabetes, hypertension and dyslipidemia. Berberis brandisiana Ahrendt (Berberidaceae) is traditionally used to treat diabetes, liver problems, wounds, arthritis, infections, swelling and tumors. It is also known to be enriched with multiple phytoconstituents including berbamine, berberine, quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, chlorogenic acid, syringic acid, p-coumaric acid, m-coumaric acid and ferulic acid. The efficacy of B. brandisiana has not been established yet in diabetes. This study has been planned to assess the antidiabetic activity of B. brandisiana in high fat diet and streptozotocin (HFD/STZ)-induced diabetes using animals. Administration of aqueous methanolic extract of B. brandisiana (AMEBB) and berbamine (Berb) for 8 weeks caused a dose dependent marked (p < 0.01) rise in serum insulin and HDL levels with a significant decline (p < 0.01) in glucose, triglycerides, glycosylated hemoglobin (HbA1c), cholesterol, LDL, LFTs and RFTs levels when compared with only HFD/STZ-administered rats. AMEBB and Berb also modulated inflammatory biomarkers (TNF-α, IL-6) and adipocytokines (leptin, adiponectin and chemerin). AMEBB (150 mg/kg and 300 mg/kg) and Berb (80 mg/kg and 160 mg/kg) treated rats showed a marked increase (p < 0.001) in catalase levels (Units/mg) in pancreas (42.4 ± 0.24, 47.4 ± 0.51), (38.2 ± 0.583, 48.6 ± 1.03) and liver (52 ± 1.41, 63.2 ± 0.51), (57.2 ± 0.58, 61.6 ± 1.24) and superoxide dismutase levels (Units/mg) in pancreas (34.8 ± 1.46, 38.2 ± 0.58), (33.2 ± 0.80, 40.4 ± 1.96) and liver (31.8 ± 1.52, 36.8 ± 0.96), (30 ± 0.70, 38.4 ± 0.81),respectively while a significant (p < 0.01) decrease in serum melondialdehyde levels (nmol/g) in pancreas (7.34 ± 0.17, 6.22 ± 0.22), (7.34 ± 0.20, 6.34 ± 0.11) and liver (9.08 ± 0.31,8.18 ± 0.29), (9.34 ± 0.10, 8.86 ± 0.24) compared to the data of only HFD/STZ-fed rats. Histopathological studies of pancreas, liver, kidney, heart and aorta revealed restoration of normal tissue architect in AMEBB and Berb treated rats. When mRNA expressions of candidate genes were assessed, AMEBB and Berb showed upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17. These findings suggest that AMEBB and Berb possess antidiabetic activity, possibly due to its effect on oxidative stress, glucose metabolism, inflammatory biomarkers and adipocytokines levels. Further upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17, demonstrated its potential impact on glucose homeostasis, insulin resistance and chronic inflammatory markers. Thus, this study provides support to the medicinal use of B. brandisiana and berbamine in diabetes.

Caryopteris odorata and its metabolite coumarin attenuate characteristic features of cardiometabolic syndrome in high-refined carbohydrate-high fat-cholesterol-loaded feed-fed diet rats.

Caryopteris odorata (D. Don) B.L. Robinson (Verbenaceae family) is an aromaric shrub traditionally used to treat diabetes and related pathologies (diabetic foot ulcer), cancer/tumors, wound healing, and inflammation. It is enriched with flavonoids and phenolics like coumarins, quercetin, gallic acid, coumaric acid, stigmasterol, α-tocopherol, and iridoids. C. odorata has been reported as having α-glucosidase, anti-inflammatory, and anti-oxidant properties. Its effectiveness in preventing cardiometabolic syndrome has not yet been assessed. This study aims to investigate the potential efficacy of C. odorata and coumarin for characteristic features of cardiometabolic syndrome (CMS), including obesity, dyslipidemia, hyperglycemia, insulin resistance, and hypertension by using high-refined carbohydrate-high fat-cholesterol (HRCHFC)-loaded feed-fed rats. Chronic administration of C. odorata and coumarin for 6 weeks revealed a marked attenuation in body and organ weights, with a consistent decline in feed intake compared to HRCHFC diet fed rats. The test materials also caused a significant reduction in the blood pressure (systolic, diastolic, and mean) and heart rate of HRCHFC-diet fed rats. Improved glucose tolerance and insulin sensitivity tests were also observed in test material administered rats compare to only HRCHFC-diet fed rats. C. odorata and coumarin-treated animals produced a marked decline in serum FBG, TC, TG, LFTs, and RFTs, while an increase in serum HDL-C levels was noticed. C. odorata and coumarin also significantly modulated inflammatory biomarkers (TNFα, IL-6), adipokines (leptin, adiponectin, and chemerin), and HMG-CoA reductase levels, indicating prominent anti-inflammatory, cholesterol-lowering, and anti-hyperglycemic potential. Administration of C. odorata and coumarin exhibited a marked improvement in oxidative stress markers (CAT, SOD, and MDA). Histopathological analysis of liver, heart, kidney, pancreas, aorta, and fat tissues showed a revival of normal tissue architecture in C. odorata and coumarin-treated rats compared to only HRCHFC-diet fed rats. These results suggest that C. odorata and coumarin possess beneficial effects against the characteristic features of CMS (obesity, insulin resistance, hypertension, and dyslipidemia) in HRCHFC feed-administered rats. These effects were possibly mediated through improved adipokines, glucose tolerance, and insulin sensitivity, the attenuation of HMG-CoA reductase and inflammatory biomarkers, and modulated oxidative stress biomarkers. This study thus demonstrates a rationale for the therapeutic potential of C. odorata and coumarin in CMS.

Cyanidin as potential anticancer agent targeting various proliferative pathways.

A natural compound cyanidin, which is a type of anthocyanin present in pigmented leaves, fruits, and flowers; distributed widely in berries, apples, and oranges possess anticancer activities, thus curing various types of cancer such as breast, liver, lung, prostate, and thyroid cancer. The article provides an insight into the potential of using a single phytochemical, cyanidin to treat various cancer types including breast, liver, lung, prostate, and thyroid cancer. Information about cyanidin and its pharmacological impact on cancer was collected from books, scientific journals, and reports through electronic data search (Web of Science, Scifinder, PubMed, Scopus, Google Scholar, Elsevier, Springer, Wiley, ACS, Science Direct, CNKI as well as Kew Plants of the Word Online) and library. Cyanidin produces its effects against cancer probably by inhibiting (RAS, MAPK) and activating (caspases-3 and P-38) innovative molecular pathways. It may cause cell cycle arrest, cell differentiation processes and changes in redox status which trigger the cytotoxic chemotherapeutic effects. However, it also optimizes the chemotherapeutic targets which are cancer cells less responsive to chemotherapy. Cancer is considered the most widely spread disease and cyanidin from natural origin provides an essential role in treatment of cancer by approaching various mechanistic pathways.

Evaluation of the Cardiovascular Effects of Coriandrum sativum and Citrus limon to Treat Arsenic-Induced Endothelial Damage and Hypertension in Rats.

Based on the vernacular reputation of Coriandrum sativum and Citrus limon to treat hypertension, this study was designed to explore the cardiovascular effects of C. sativum (CS) and C. limon (CL) on arsenic-induced hypertension and endothelial damage. Hypertension was induced by arsenic (100 ppm) in drinking water. The crude methanolic extracts of CS and CL were tested for in vivo and in vitro activities using Power Lab. High performance liquid chromatography analysis of CS and CL showed the presence of phenolic compounds. In anesthetized rats, CS (50 mg) and CL (10 mg) showed a marked decrease in blood pressure of 51% and 35%, respectively. Similarly, ascorbic acid (10 mg) also showed a decreased blood pressure (41%). The CS and CL caused complete relaxation (0.003−5 mg/mL) against phenylephrine (1µM) and high K+ (80 mM)-induced contraction. The CS and CL, independently and in combination, exhibited marked (p < 0.001) attenuation in the blood pressure of the arsenic-induced hypertensive rats when compared with the controls. The beneficial effects of the CS and CL were also observed on lipid peroxidation and eNOS. These data suggest that CS and CL possess significant antihypertensive activity, possibly mediated via endothelium protection, and anti-oxidant effects. Thus, this study provides a rationale for the medicinal use of CS and CL in hypertension and also against arsenic-induced cardiovascular complications.

Ajuga bracteosa Exerts Antihypertensive Activity in l-NAME-Induced Hypertension Possibly through Modulation of Oxidative Stress, Proinflammatory Cytokines, and the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway.

Ajuga bracteosa has been used in traditional medicine to treat hypertension and other ailments. The present study has been designed to investigate the beneficial effects of A. bracteosa in l-nitro arginine methyl ester (l-NAME)-induced hypertensive rats. Hypertension was induced by intraperitoneal injection of l-NAME (185 µmol kg-1 i.p.). The aqueous methanol extract of A. bracteosa (AMEAB, 250 and 500 mg kg-1) and coumarin (30 and 70 mg kg-1) were administered orally from day 8 to day 35 of the study. In vivo antihypertensive activity was assessed by measuring the blood pressure using a PowerLab data system. The effects of the AMEAB and coumarin on nitric oxide (NO), cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), the tumor necrosis factor (TNF-α), and oxidative stress markers were also assessed using kit methods. Phytochemical profiling of the AMEAB was carried out through high-performance liquid chromatography (HPLC) where quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, syringic acid, p-coumaric acid, and ferulic acid were labeled as plant constituents including coumarin. The AMEAB and coumarin significantly reduced blood pressure at the tested doses of 500 and 70 mg kg-1, respectively. Serum levels of NO and cGMP were found to be significantly increased in AMEAB- and coumarin-treated groups when compared with only l-NAME-challenged rats. In addition, a marked decrease was noticed in the serum concentrations of proinflammatory cytokines (IL-6 and TNF-α) in AMEAB- and coumarin-treated rats. Moreover, in AMEAB- and coumarin-treated animals, a noticeable improvement was observed in the levels of antioxidant enzymes including catalase, superoxide dismutase, and malonaldehyde, and the total oxidant status when compared with those of only l-NAME-challenged rats. The data of real-time polymerase chain reaction (RT-PCR) experiments supported that the antihypertensive and anti-inflammatory activities of the AMEAB and coumarin are possibly mediated through modulation of endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme (ACE), nuclear factor (NF)-kB, and COX-2 gene expressions. This study concludes that A. bracteosa possesses an antihypertensive effect mediated through the modulation of the antioxidant, anti-inflammatory, and NO/cGMP pathways, thus providing a rationale to the antihypertensive use of A. bracteosa in traditional medicine.

Polycystic Ovary Syndrome: A Disorder of Reproductive Age, Its Pathogenesis, and a Discussion on the Emerging Role of Herbal Remedies.

Polycystic ovary syndrome (PCOS) is a very common, complex, and heterogeneous endocrine disorder of women that involves a combination of environmental and genetic factors. PCOS affects women of growing age particularly at the early to late reproductive stage (15-35 years). Currently, PCOS affects 1 in every 10 women worldwide. It is characterized majorly by a raised level of androgens such as testosterone and a large number of ovarian cysts (more than 10) that cause anovulation, infertility, and irregular menstrual cycle. PCOS is also related to other endocrine and metabolic abnormalities, such as obesity, hirsutism, acne, diabetes, insulin resistance, and glucose impairment. PCOS can be treated with allopathic, ayurvedic, and natural or herbal medications along with lifestyle modifications. Herbal medicines remained in demand for numerous reasons such as high cost and side effects associated with the use of allopathic medicine and our traditional norms, which have helped humans to use more herbal products for their health benefits. Estrogenic and nonestrogenic phytochemicals present in various plant species such as Glycyrrhiza glabra L. [Fabaceae], Aloe vera (L.) Burm. f. [Asphodelaceae], Silybum marianum (L.). Gaertn. [Asteraceae], Serenoa repens (W.Bartram) Small [Arecaceae], Actaea racemosa L. [Ranunculaceae], and Angelica sinensis (Oliv.) Diels [Apiaceae] are effective and harmless. Herbal medicines are found to be cost-effective, efficacious, and a highly esteemed source of management/treatment for PCOS than allopathic medicines. In this literature review, diagnosis, signs, and symptoms of PCOS; causes of hormonal imbalance; and risk factors associated with PCOS and their management are discussed briefly, and the focus was to find out the role of herbal remedies in PCOS management.

Bromocriptine therapy: Review of mechanism of action, safety and tolerability.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long-term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia-associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs.

Promising role of polymeric nanoparticles in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory illness caused by an autoimmune disorder of synovial membrane resulting in synovial membrane dysfunction. The available treatment particularly focuses on inhibiting macrophage proliferation and reducing the generation of pro-inflammatory cytokines. However, therapeutic success of current treatment options at targeted site is limited; therefore, development of promising therapeutic strategy is the need of time that may provide better targeted delivery of drug with added safety. In development of precision medicine to manage RA, nanotechnology is a viable option to be considered. Recent research using nanoparticles for the treatment of RA, particularly polymeric nanoparticles, has been discussed in this article. Using polymeric nanoparticles as a therapeutic method has shown considerable promise of enhancing treatment success over standard medications used in routine. It is exclusively evident that the viability of using nanoparticles is mainly owed due to their biocompatibility, chemical stability, controlled drug release, and selective drug delivery to inflamed tissues in RA model animals. The current analysis focuses on the critical design characteristics of RA-targeted nanotechnology-based strategies in quest of better therapeutic strategies for RA, and to identify leading polymer as the most effective medications in RA therapy.

Knowledge, Attitude, Practice, Behavior and Risk Perception of COVID-19 Pandemic among Medical and non-Medical University Students.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) pandemic has substantially affected students around the globe due to the closure of educational institutes. However, student involvements and contributions are important in combating the disease; for this reason, the current study was designed to assess the knowledge-attitude-practice (KAP), preventive behavior, and risk perception among university students. METHODS: A cross-sectional survey-based study was conducted among medical and non-medical university students, from April 1 to June 30, 2020. The 68-item questionnaire was used to evaluate responses using statistical approaches (Student's t-test, regression-analysis, and co-relation analysis) by considering a P-value <0.05 as statistically significant. RESULTS: A total of 503 university students (medical and nonmedical) were selected, where majority of participants were females (83%) and 64.5% were of age ranged from 16 to 21 years old. The participants (80%) reported good disease knowledge with a mean score of 12.06 ± 1.75, which substantially higher among medical students (P < 0.05). Most of the respondents (72%) believed that COVID-19 will be effectively controlled through precautionary measures. In correlation subgroup analysis, a significant relationship (P = 0.025) between knowledge and positive attitude were indicated. Fear and knowledge of COVID-19 emerged as strong predictors (P < 0.001) of preventive behaviors towards disease. CONCLUSION: This study demonstrated satisfactory knowledge, positive attitudes, and suitable practices among students toward COVID-19. University students can be involved in public education to aid the health authorities in achieving the targets of educational campaigns with maximum population coverage.

Ziziphus Oxyphylla hydro-methanolic extract ameliorates hypertension in L-NAME induced hypertensive rats through NO/cGMP pathway and suppression of oxidative stress related inflammatory biomarkers.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphus Oxyphylla belongs to family Ziziphus and has been used traditionally in hypertension. It is enriched with quercetin and kaempferol derivatives, catechin and cyclopeptide alkaloids. AIM: The current research evaluates the antihypertensive potential of aqueous methanolic extract of Z. oxyphylla (AMEZO) in NG-nitro-L-arginine methyl ester (LNAME) induced hypertension in rats. MATERIAL AND METHODOLOGY: Phytochemical analysis of AMEZO was carried out using high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS/MS). Antihypertensive activities of AMEZO (200 and 400 mg/kg) and Kaempferol were assessed in L-NAME (185 µmol/kg, intraperitoneal) injected hypertensive rats. In normotensive rats, blood pressure was assessed using Power Lab data system. Serum and tissue samples were preserved for estimation of nitric oxide (NO), Cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), tumor necrosis factor (TNF- α) and oxidative stress markers respectively. mRNA levels of eNOS, ACE, COX-2 and NF-kB genes were assessed through qPCR. RESULTS: The HPLC and ESI-MS/MS identified kaempferol, quercetin, catechin, ceanothic acid, zizybernalic acid and oxyphylline F. Chronic administration of AMEZO and kaempferol in L-NAME induced hypertensive rats significantly (p < 0.001) reduced systolic, diastolic and mean blood pressure. AMEZO and kaempferol caused meaningfully improved (p < 0.001) serum NO and cGMP levels. AMEZO administration also noticeably decrease the elevated IL-6 and TNF- α concentration in hypertensive animals. Administration of AMEZO and kaempferol also improved oxidative stress markers (MDA, CAT, SOD, GSH). The antihypertensive activity of AMEZO also resulted in upregulation of eNOS and downregulation of ACE. CONCLUSION: These data depict that AMEZO and kaempferol showed antihypertensive activity in LNAME induced hypertensive rats possibly mediated through improvement in NO and cGMP levels, modulation of mRNA expression of eNOS, ACE, COX-2 and NF-kB and suppression of oxidative stress related inflammatory markers, proposing a defensive role in cardiovascular diseases.

Pharmacological evaluation of Euphorbia hirta, Fagonia indica and Capparis decidua in hypertension through in-vivo and in vitro-assays.

OBJECTIVE: This study determines the efficacy and probable underlying mode of action to the folk usage of Euphorbia hirta, Fagonia indica and Capparis decidua in hypertension. METHODS: The aqueous-methanol extracts of E. hirta (EH.Cr), F. indica (FI.Cr) and C. decidua (CD.Cr) were tested for antihypertensive effects in rats using non-invasive and in-vasive blood pressure measuring apparatus. In-vitro assays were carried out using isolated rat aortae using PowerLab station. RESULTS: EH.Cr, FI.Cr and CD.Cr at 500 mg/kg (orally) caused a fall in the mean systolic blood pressure in arsenic-induced hypertensive and normotensive rats, similar to nifedipine. In rat aortae, EH.Cr, CD.Cr and FI.Cr reversed low (20 mM), high (80 mM) K+ and phenylephrine (P.E)-driven contractions, while F. indica partially inhibited high K+ contractions. In the presence of TEA, F. indica remained unable to relax low K+ contractions. EH.Cr and CD.Cr moved Ca++ concentrations response curves to the right, like nifedipine. All fractions of EH.Cr and CD.Cr except aqueous, pet-ether and chloroform fractions of FI.Cr displayed Ca++ antagonistic activity. FI.Cr, its ethyl acetate and aqueous fraction exhibited TEA-sensitive potassium channel activation. On baseline tension, test materials also produced phentolamine-sensitive vasospasm. CONCLUSION: E. hirta, F. indica and C. decidua possess antihypertensive activity in arsenic-induced hypertensive rats possibly mediated via endothelium-dependent vasorelaxation. In normotensive rats, E. hirta and C. decidua showed antihypertensive activities through endothelium-dependent and Ca++ antagonistic pathways, while F. indica exhibited potassium channel activation and Ca++ antagonistic like effects in its vasorelaxation. Additional weaker vasospastic effects were derived through α-adrenergic like pathways.

Chemical characterisation and appraisal of antidiabetic potential of Terminalia citrina extract in streptozotocin induced hyperglycaemia in Wistar rats.

The current research was aimed to evaluate the antidiabetic activity of Terminalia citrina methanolic extract (TCME) by streptozotocin-induced diabetes in male Wistar rats. TCME exhibited better in-vitro antioxidant and alpha-amylase inhibitory activity as compared to other tested extracts. TCME at 250, 500, and 750 mg/kg showed notable (p < .05) antidiabetic potential by lowering fasting blood glucose level, restoring lipid level, serum amylase, HbA1c, kidney, and liver function tests as coevidenced from histological findings of the liver, pancreas, and kidney. TCME remarkably reinstated the antioxidant enzymatic activities (CAT: 0.181 ± 0.011 IU/mg protein, SOD: 21.45 ± 1.53 IU/mg protein) and reduced lipid peroxidation level (40.60 ± 2.41 µM/mg protein) in the liver and kidney tissue of diabetic rats at 750 mg/kg dose. The acute and subacute oral toxicity study of TCME exhibited no clinical toxicity signs and mortality. Its GC-MS spectrum unveiled the existence of 10-octadecenoic acid and other compounds which might have contributed to antidiabetic potential.

Hydroethanolic Extract of A. officinarum Hance Ameliorates Hypertension and Causes Diuresis in Obesogenic Feed-Fed Rat Model.

Alpinia officinarum Hance (Zingiberaceae) has been used widely in traditional Chinese and Ayurvedic medicines. Its folkloric uses include relieving stomach ache, treating cold, improving the circulatory system, and reducing swelling. Its effectiveness and mechanism of antihypertension in obesity-induced hypertensive rats have not been studied yet as per our knowledge. This study has been designed to provide evidence of underlying mechanisms to the medicinal use of A. officinarum as a cardiotonic using an obesity-induced hypertension model in rats. Chronic administration of A. officinarum caused a marked reduction in the body weight gain and Lee index of rats compared to the obesogenic diet-fed rats. Its administration also caused attenuation in blood pressure (systolic, diastolic, and mean), serum total cholesterol, triglyceride, and leptin, while an increase in serum HDL and adiponectin levels was noticed. The catalase and superoxide dismutase enzymatic activities were found to be remarkable in the serum of A. officinarum-treated animal groups. A. officinarum showed mild to moderate diuretic, hepatoprotective, and reno-protective effects. The A. officinarum-treated group showed less mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase while the mRNA expression of peroxisome proliferator-activated receptor and mRNA expression of cholesterol 7 alpha-hydroxylase were raised in comparison to the hypertensive group of rats evaluated by quantitative real-time polymerase chain reaction. These findings show that A. officinarum possesses antihypertensive and diuretic activities, thus providing a rationale to the medicinal use of A. officinarum in cardiovascular ailments.

In Vitro Antioxidant Activities and the Therapeutic Potential of Some Newly Synthesized Chalcones Against 4-Acetaminophenol Induced Hepatotoxicity in Rats.

The lack of safety and efficacy of existing hepatoprotective agents urge the need to explore novel hepatoprotective agents. The research work was planned to study the therapeutic potential of some newly synthesized chalcones against 4-acetaminophenol induced hepatotoxicity in rats. Male albino rats (N = 30) were divided into 6 groups of 5 animals each i.e. group I; Toxic control (4-acetaminophenol), group II; normal control (Normal saline), group III; Positive control (silymarin; 50 mg/kg bw) and groups IV-VI (test groups) treated with 3 chalcone analogues i-e 3a, 3f & 3 g (100, 150, 150 mg/kg bw, respectively). All the study group animals were administered with 4-acetaminophenol to induce hepatotoxicity except normal control. Following hepatotoxicity induction, test group animals were administered with selected doses of test compounds and toxic group animals left untreated. Liver enzymes including ALT, AST, ALP and serum bilirubin were determined photometrically. Antioxidant activities of test compounds were also determined. Histopathological examination of liver biopsies was also carried out through H & E staining. The test chalcones (3a, 3f & 3 g) significantly decreased the levels of liver enzymes and serum bilirubin toward normal and the pattern of results in the test group animals were comparable to silymarin administered animals indicating the hepatoprotective potential of test compounds. Moreover, the test chalcones (3a, 3f & 3 g) antagonized the effect of 4-acetaminophenol and thus, raised the catalase (CAT) and superoxide dismutase (SOD) while decreased the malondialdehyde (MDA) in experimental animals. The test chalcones (3a, 3f & 3 g) on histological examination of liver showed improvement of tissue morphology. The study concluded that the tested compounds have antioxidant potential and may act as hepatoprotective agent. However, in-depth studies are required to validate their safety and to elucidate the exact mechanism of action.

A flavonoid driven phyto-pharmacological effects of Capparis decidua Edgew. in rodents.

This study elicits the underlying mechanism(s) of Capparis decidua when used for different gut disorders. HPLC chromatogram of C. decidua extract (CD.Cr) and its respective fractions showed a variety of phytochemicals of which, kaempferol being in a high proportion. In mice, CD.Cr at doses of 70 and 150 mg/kg enhanced the wet feces output to 33 and 44% respectively as compared to carbachol (47.6%), while doses of 500 and 700 mg/kg, presented 41 and 70% safety against castor oil-driven diarrhea, respectively. Its flavonoid constituent, kaempferol at doses of (50 and 100 mg/kg) produced 51.7 and 82% safety when compared to nifedipine which provided 95% safety at dose of 40 mg/kg against castor oil-driven diarrhea like loperamide. In isolated jejunum preparations, C. decidua extract and its respective fractions (except pet-ether) produced atropine-sensitive inhibitory effects, whereas kaempferol and nifedipine showed atropine insensitive effects. Against high K+-induced contractions, C. decidua's fractions and kaempferol both exhibited a concentration-related non-specific inhibition while displacing the Ca++ -CRCs to right-ward with suppression in maximal response like nifedipine. In isolated rat ileal preparations, CD.Cr and respective fractions elicited atropine-sensitive gut excitatory responses. In summary, this article reports C. decidua's laxative effect through cholinergic receptor activation as well as its antidiarrheal effects, where its flavonoid constituent kaempferol produces Ca++ antagonist like activity, thus justifying C. decidua folk use in constipation and diarrhea.