Moringa oleifera: An Updated Comprehensive Review of Its Pharmacological Activities, Ethnomedicinal, Phytopharmaceutical Formulation, Clinical, Phytochemical, and Toxicological Aspects.

Moringa oleifera, also known as the "tree of life" or "miracle tree," is classified as an important herbal plant due to its immense medicinal and non-medicinal benefits. Traditionally, the plant is used to cure wounds, pain, ulcers, liver disease, heart disease, cancer, and inflammation. This review aims to compile an analysis of worldwide research, pharmacological activities, phytochemical, toxicological, and ethnomedicinal updates of Moringa oleifera and also provide insight into its commercial and phytopharmaceutical applications with a motive to help further research. The scientific information on this plant was obtained from various sites and search engines such as Scopus, Pub Med, Science Direct, BMC, Google Scholar, and other scientific databases. Articles available in the English language have only been referred for review. The pharmacological studies confirm the hepatoprotective, cardioprotective, and anti-inflammatory potential of the extracts from the various plant parts. It was found that bioactive constituents are present in every part of the plant. So far, more than one hundred compounds from different parts of Moringa oleifera have been characterized, including alkaloids, flavonoids, anthraquinones, vitamins, glycosides, and terpenes. In addition, novel isolates such as muramoside A&B and niazimin A&B have been identified in the plant and have potent antioxidant, anticancer, antihypertensive, hepatoprotective, and nutritional effects. The traditional and nontraditional use of Moringa, its pharmacological effects and their phytopharmaceutical formulations, clinical studies, toxicity profile, and various other uses are recognized in the present review. However, several traditional uses have yet to be scientifically explored. Therefore, further studies are proposed to explore the mechanistic approach of the plant to identify and isolate active or synergistic compounds behind its therapeutic potential.

Promises of phytochemical based nano drug delivery systems in the management of cancer.

Cancer is the leading cause of human disease and death worldwide, accounting for 7.6 million deaths per year and projected to reach 13.1 million by 2030. Many phytochemicals included in traditional medicine have been utilized in the management of cancer. Conventional chemotherapy is generally known to be the most effective treatment of metastatic cancer but these cancerous cells might grow resistant to numerous anticancer drugs over time that resulting in treatment failure. This review tried to portray the advancement in the anticancer and chemopreventive effects of several phytochemicals and some of its members encapsulated in the nano-based delivery system of the drug. It comprises the issue associated with limited use of each phytoconstituents in human cancer treatment are discussed, and the benefits of entrapment into nanocarriers are evaluated in terms of drug loading efficiency, nanocarrier size, release profile of the drug, and in vitro and/or in vivo research and treatment testing, such as cytotoxicity assays and cell inhibition/viability.

Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg i.p.)- induced neuropathic pain in Wistar rats.Methods: Docking simulation studies were done on the three-dimensional (3D) structure of the GABAA and PPAR γ receptor for the binding of EA as well as punicalagin docking studies on TNF-α, and IL-6. The Present Study conceptualized a test battery to evaluate the behavioral, biochemical and histological changes.Results: Vincristine -induced significant cold allodynia, mechanical hyperalgesia, and functional deficit on 12th and 21st days. It also increased in the levels of TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), and MPO (Myeloperoxidase). Administration of PFE (100 and 300 mg/kg, p.o.), EA (50 mg/kg), and gabapentin (100 mg/kg) attenuated Vincristine-induced behavioral and biochemical changes significantly (P < .05). PFE showed better antinociceptive activity to EA. The histopathological evaluation also revealed the protective effects of PFE. Pretreatment of bicuculline (selective antagonist of GABAA receptors) reversed antinociceptive action of PFE, but administration of γ aminobutyric acid potentiated the action of PFE. PPAR-γ antagonist BADGE did not modify the effect of PFE. Docking results revealed that EA properly positioned into GABA and PPARγ binding site and acts as a partial agonist. Docking score of Punicalagin found to be - 9.02 kcal/mol and - 8.32 kcal/mol on IL-6 and TNFα respectively.Discussion: Conclusively, the attenuating effect of PFE may be attributed to the GABAergic system, cytokine inhibition, and anti-inflammatory activities.

Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda.

BACKGROUND: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda. METHODS AND FINDINGS: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care. CONCLUSIONS: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.

Tyrosine hydroxylase deficiency-Clinical insights and a novel deletion in TH gene in an Indian patient.

Tyrosine hydroxylase deficiency is a rare autosomal recessive, treatable disorder of neurotransmission. Fewer than 100 cases have been reported so far. We present a case of a 10-month-old infant who was symptomatic since 5 months of age and who received an initial diagnosis of infantile tremor syndrome. She presented with rest tremor, decreased facial expression, global hypokinesia, and later on with oculogyric crisis and dystonia. This diagnosis was revised after confirmation of tyrosine hydroxylase deficiency by CSF neurotransmitter analysis. Genetic studies revealed one previously reported missense variant, p.Thr399Met, and another large deletion starting upstream of exon 1 and encompassing exon 1. She was started on treatment with escalating doses of L-Dopa/Carbidopa, with folinic acid supplementation. At 3.5 years of age, her cognitive functioning and development is appropriate for age. There is complete subsidence of dystonia and oculogyric episodes. She has occasional chorieform movements which appear to be drug related.

Hypertension control in integrated HIV and chronic disease clinics in Uganda in the SEARCH study.

BACKGROUND: There is an increasing burden of hypertension (HTN) across sub-Saharan Africa where HIV prevalence is the highest in the world, but current care models are inadequate to address the dual epidemics. HIV treatment infrastructure could be leveraged for the care of other chronic diseases, including HTN. However, little data exist on the effectiveness of integrated HIV and chronic disease care delivery systems on blood pressure control over time. METHODS: Population screening for HIV and HTN, among other diseases, was conducted in ten communities in rural Uganda as part of the SEARCH study (NCT01864603). Individuals with either HIV, HTN, or both were referred to an integrated chronic disease clinic. Based on Uganda treatment guidelines, follow-up visits were scheduled every 4 weeks when blood pressure was uncontrolled, and either every 3 months, or in the case of drug stock-outs more frequently, when blood pressure was controlled. We describe demographic and clinical variables among all patients and used multilevel mixed-effects logistic regression to evaluate predictors of HTN control. RESULTS: Following population screening (2013-2014) of 34,704 adults age ≥ 18 years, 4554 individuals with HTN alone or both HIV and HTN were referred to an integrated chronic disease clinic. Within 1 year 2038 participants with HTN linked to care and contributed 15,653 follow-up visits over 3 years. HTN was controlled at 15% of baseline visits and at 46% (95% CI: 44-48%) of post-baseline follow-up visits. Scheduled visit interval more frequent than clinical indication among patients with controlled HTN was associated with lower HTN control at the subsequent visit (aOR = 0.89; 95% CI 0.79-0.99). Hypertension control at follow-up visits was higher among HIV-infected patients than uninfected patients to have controlled blood pressure at follow-up visits (48% vs 46%; aOR 1.28; 95% CI 0.95-1.71). CONCLUSIONS: Improved HTN control was achieved in an integrated HIV and chronic care model. Similar to HIV care, visit frequency determined by drug supply chain rather than clinical indication is associated with worse HTN control. TRIAL REGISTRATION: The SEARCH Trial was prospectively registered with ClinicalTrials.gov : NCT01864603.

Evaluation of effect of alcoholic extract of heartwood of Pterocarpus marsupium on in vitro antioxidant, anti-glycation, sorbitol accumulation and inhibition of aldose reductase activity.

Rising popularity of phytomedicines in various diseased conditions have strengthened the significance of plant-research and evaluation of phytoextracts in clinical manifestations. Pterocarpus marsupium Roxb., a medicinal plant, known for its anti-oxidant and anti-diabetic activity is a rich source of phytochemicals with antihyperglycemic and antihyperlipidemic activities. However, its possible role in diabetic complications is not evaluated yet. The present study explores the possible role of alcoholic extract of heartwood of P. marsupium in the treatment of long-term diabetic complications. The alcoholic extract of P. marsupium was evaluated for advanced glycation-end-products formation, erythrocyte sorbitol accumulation and rat kidney aldose reductase enzyme inhibition at the concentration of 25-400 µg/ml using in-vitro bioassays. Also the phytoextract at the concentration of 10-320 µg/ml was evaluated for its antioxidant potential by in-vitro antioxidant assays which includes, determination of total phenol content; reducing power assay; nitric oxide scavenging activity; superoxide radical scavenging activity; total antioxidant capacity; total flavonoid content; DPPH scavenging activity; and hydrogen peroxide scavenging activity. The alcoholic extract of P. marsupium across varying concentrations showed inhibitory effect as evident by IC50 on advanced glycation-end-products formation (55.39 µg/ml), sorbitol accumulation (151.00 µg/ml) and rat kidney aldose reductase (195.88 µg/ml). The phytoextract also exhibited high phenolic and flavonoid contents with promising antioxidant potential against the antioxidant assays evaluated. The present investigation suggests that the phytoextract showed prominent antioxidant, antiglycation property and, inhibited accumulation of sorbitol and ALR enzyme, thus promising a beneficial role in reducing/delaying diabetic complications.

Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

OBJECTIVE: This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. MATERIALS AND METHODS: TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. RESULTS: TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. CONCLUSIONS: Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.

Protective effect of Lannea coromandelica Houtt. Merrill. against three common pathogens.

BACKGROUND: Ayurvedic text reports suggested Lannea coromandelica is used in various microbial origin disorders like dysentery, sore eyes and leprosy, genital wounds. OBJECTIVE: The present study was designed to investigate the antimicrobial effect of L. coromandelica Houtt. Merrill. (Anacardiaceae) on microbes which cause female reproductive tract infection. MATERIALS AND METHODS: Ethanolic and aqueous bark extract (Ext.) of L. coromandelica were screened against strains of Streptococcus pyogens, Staphylococcus aureus, and Candida albicans. Antimicrobial assay had been done with agar well diffusion method. RESULTS: Ethanolic extracts [100% (16 mg), 75% (12 mg) and 50% (8 mg)] of L. coromandelica exhibited zone of inhibition (ZI) 19.21 mm, 18.45 mm, 16.41 mm and 18.12 mm, 17.35 mm, 16.35 mm against S. aureus and S. pyogens, respectively. However, only 100% and 75% ethanolic extract showed (ZI-19.18 mm, 16.29 mm) activity against C. albicans. Nevertheless, aqueous extract (100%) showed higher antifungal activity (ZI-16.97 mm). Ciprofloxacin and amphotericin B were used as a standard drugs in the present study. CONCLUSION: The results demonstrated that L. coromandelica Houtt. Merrill. have antibacterial activity against S. pyogens, S. aureus and antifungal property against C. albicans. Our findings corroborate the ethnobotanical use of L. coromandelica in traditional medicine system (Ayurveda) of India.

Attenuating effect of standardized fruit extract of Punica granatum L in rat model of tibial and sural nerve transection induced neuropathic pain.

BACKGROUND: Injury to a nerve is the most common reason of acquired peripheral neuropathy. Therefore, searching for effective substance to recover of nerve after injury is need of present era. The current study investigates the protective potential of Standardized Fruit Extract of Punica granatum L (PFE) [Ellagic acid (41.6%), Punicalagins (10%), Granatin (5.1%)] in Tibial & Sural Nerve Transection (TST) induced neuropathic pain in rats. METHODS: TST was performed by sectioning tibial and sural nerve portions of the sciatic nerve and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint brush & Walking Track tests were performed to assess cold allodynia; mechanical heat, hyperalgesia and dynamic mechanical allodynia & tibial functional index respectively. The levels of TNF-α, TBARS, GSH and Nitrite were measured in the sciatic nerve as an index of inflammation & oxidative stress. RESULTS: TST led to significant development of cold allodynia; mechanical and heat hyperalgesia; dynamic mechanical allodynia; functional deficit in walking along with rise in the levels of TBARS, TNF-α, GSH and Nitrite. Administrations of PFE (100 & 300 mg/kg oral), significantly attenuate TST induced behavioral & biochemical changes. Pretreatments of BADGE (120 mg/kg IP) a PPAR-γ antagonist and nitric oxide precursor L-arginine (100 mg/kg IP) abolished the protective effect of PFE. Whereas, pretreatment of L-NAME (5 mg/kg IP) a NOS inhibitor significantly potentiated PFE's protective effect of PFE. CONCLUSION: PFE shown to have attenuating effect in TST induced neuropathic pain which may be attributed to potential PPAR-gamma agonistic activity, nitric oxide inhibitory, anti-inflammatory and anti oxidative actions.

Animal models of neuropathic pain.

Animal models are pivotal for understanding the mechanism of neuropathic pain and development of effective therapy for its optimal management. A battery of neuropathic pain models has been developed to simulate the clinical pain conditions with diverse etiology. The present review exhaustively discusses the methodology, behavioral alterations, limitations, and advantages of about 40 different animal models of neuropathic pain along with their modifications. Development of these models has contributed immensely in understanding the chronic pain and underlying peripheral as well as central pathogenic mechanisms. Furthermore, research has resulted in the development of new therapeutic agents for neuropathic pain management, and the preclinical data obtained using these animal models have been successively translated to effective pain management in clinical setup also. As each animal model has been created with specific methodology and results tend to vary largely with the slight changes related to methodology, therefore, it is essential that data from different models should be reported and interpreted in the context of the specific pain model.