Antidiabetic Potential of Commonly Available Fruit Plants in Bangladesh: Updates on Prospective Phytochemicals and Their Reported MoAs.

Diabetes mellitus is a life-threatening disorder affecting people of all ages and adversely disrupts their daily functions. Despite the availability of numerous synthetic-antidiabetic medications and insulin, the demand for the development of novel antidiabetic medications is increasing due to the adverse effects and growth of resistance to commercial drugs in the long-term usage. Hence, antidiabetic phytochemicals isolated from fruit plants can be a very nifty option to develop life-saving novel antidiabetic therapeutics, employing several pathways and MoAs (mechanism of actions). This review focuses on the antidiabetic potential of commonly available Bangladeshi fruits and other plant parts, such as seeds, fruit peals, leaves, and roots, along with isolated phytochemicals from these phytosources based on lab findings and mechanism of actions. Several fruits, such as orange, lemon, amla, tamarind, and others, can produce remarkable antidiabetic actions and can be dietary alternatives to antidiabetic therapies. Besides, isolated phytochemicals from these plants, such as swertisin, quercetin, rutin, naringenin, and other prospective phytochemicals, also demonstrated their candidacy for further exploration to be established as antidiabetic leads. Thus, it can be considered that fruits are one of the most valuable gifts of plants packed with a wide spectrum of bioactive phytochemicals and are widely consumed as dietary items and medicinal therapies in different civilizations and cultures. This review will provide a better understanding of diabetes management by consuming fruits and other plant parts as well as deliver innovative hints for the researchers to develop novel drugs from these plant parts and/or their phytochemicals.

Evaluation of Wound-Healing and Antioxidant Effects of Marantodes pumilum (Blume) Kuntze in an Excision Wound Model.

Marantodes pumilum (MP) is a great source of herbal medicine used traditionally by both men and women for various purposes. MP may have potential wound-healing effects due to its diverse biological properties. An extensive study was conducted in a normal male rat model for determining the effects of MP var. pumila (MPvp) and var. alata (MPva) on the wound healing process. Here, 126 male Sprague-Dawley rats were divided randomly into seven groups as follows: sham-operated (SH), vehicle dressing (VD), flavine dressing (FD), MPvp leaves (PL), MPvp roots (PR), MPva leaves (AL), and MPva roots (AR). The parameters studied were the percentage of wound contraction, histomorphology study by hematoxylin and eosin (H&E), Masson-Goldner trichrome (MGT), and immunohistochemistry (IHC) staining. In addition, the levels of enzymatic antioxidants and malondialdehyde were also measured in the wound tissue homogenates. Wounds treated with extracts (PL, PR, AL, and AR) showed significantly faster healing (p < 0.05) compared to untreated and control groups (SH, VD, and FD). Histological analysis among MP-treated groups revealed better re-epithelialization, higher collagen deposition, enhanced fibronectin content and fibroblast cells, and higher fiber transformation from collagen-III to collagen-I, accompanied with a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. MP has antioxidant effects that may enhance wound healing in the rat model.

Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension.

INTRODUCTION: Sexual dysfunction in hypertensive women is an often-neglected subject despite a reported prevalence of 42.1%. Although few reviews exist, a definitive relationship between hypertension and sexual dysfunction in women has not been clearly established. AIM: To review the existing literature to definitively examine sexual dysfunction in women with hypertension, in both treated and untreated subjects. METHODS: We performed a systematic search for published literature of 3 electronic databases (Scopus, EBSCOhost Medline Complete, and Cochrane Library) in August 2018. The search terms with relevant truncation and Boolean were developed according to a population exposure-comparator-outcome model combining pilot searches. The quality of included studies was assessed with the McMaster Critical Review Form for Quantitative Studies. Initial search, limited to the English language, included a total of 2,198 studies. 31 studies (18,260 subjects) met our inclusion criteria and were included in the review. Sexual dysfunction in these studies was measured using different tools. We extracted information of study setting, country, number of subjects, participants' age and blood pressure, comparators, and outcome. We ran a meta-analysis on the presence of sexual dysfunction as an outcome from the following comparisons: (i) hypertensive vs normotensive (ii) treated vs untreated hypertension, and (iii) exposure vs absence of specific class of anti-hypertensive drug. MAIN OUTCOME MEASURES: Women with sexual dysfunction and hypertension were included. RESULTS: We found significant sexual dysfunction in women with hypertension compared with the normotensive group (pooled odds ratio [OR] = 2.789, 95% CI = 1.452-5.357, P = .002). However, there was no statistical difference of sexual dysfunction in women with treated or untreated hypertension (OR = 1.229, 95% CI = 0.675-2.236, P = .5). Treatment with alpha-/beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics resulted in no statistical difference in sexual dysfunction in hypertensive women. CLINICAL IMPLICATIONS: Because sexual dysfunction is prevalent in women with hypertension, it is imperative to address the underlying medical condition to manage this important clinical problem. STRENGTH & LIMITATIONS: Many studies had to be excluded from the meta-analysis, due to unavailability and incompleteness of data. Nevertheless, results of the review are useful to derive recommendations for alerting physicians of the need to routinely assess the sexual functioning of women with hypertension. CONCLUSION: We conclude that women with hypertension are at increased risk for sexual dysfunction, and our findings imply that evaluation for sexual dysfunction needs to be part of the clinical management guidelines for women with hypertension. Choy CL, Sidi H, Koon CS, et al. Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension. J Sex Med 2019;16:1029-1048.

Therapeutic effect of Vitamin E in preventing bone loss: An evidence-based review.

The present review explored the anti-inflammatory and immunomodulatory properties of vitamin E, which has protective action against osteoporosis. A systematic review of the literature was conducted to identify the published bone studies on vitamin E. The studies included inflammatory or immunology-related parameters. Medline and Scopus databases were searched for relevant studies published from 2005 till 2015. Research articles published in English and confined to the effect of vitamin E on bone were included. It is pertinent to mention that these studies took into consideration inflammatory or immunology parameters including interleukin (IL)-1, IL-6, receptor activator of nuclear factor kappa-B ligand (RANKL), inducible nitric oxide synthases (iNOS), serum amyloid A (SAA), e-selection and high-sensitivity C-reactive protein (hs-CRP). An extended literature search yielded 127 potentially relevant articles with seven articles meeting the inclusion and exclusion criteria. Another recent article was added with the total number accounting to eight. All these included literature comprised five animal studies, one in-vitro study and two human studies. These studies demonstrated that vitamin E, especially tocotrienol, was able to alleviate IL-1, IL-6, RANKL, iNOS and hs-CRP levels in relation to bone metabolism. In conclusion, vitamin E exerts its anti-osteoporotic actions via its anti-inflammatory and immunomodulatory effects.

Demethylbelamcandaquinone B (Dmcq B) Is the Active Compound of Marantodes pumilum var. alata (Blume) Kuntze with Osteoanabolic Activities.

Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17ß-estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-κß ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.

Effects of standardized quassinoid-rich Eurycoma longifolia extract in a rat model of osteoporosis due to testosterone deficiency: A densitometric, morphometric and biomechanical study.

BACKGROUND: Eurycoma longifolia (EL) is a well-known aphrodisiac herb for men. Recently, the crude extract of EL was reported to possess anti-osteoporotic activities. OBJECTIVE: This study aims to determine the bone protective effects of the standardized quassinoid-rich EL extract in testosterone-deficient rat model. METHODS: Ninety-six intact male Sprague-Dawley rats were randomized into baseline, sham, orchidectomized, and chemically castrated groups. Chemical castration was performed via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomized and degarelix-induced rats were administered with vehicle, intramuscularly injected with testosterone once a week, or orally supplemented with EL extract at doses of 25 mg/kg, 50 mg/kg or 100 mg/kg daily for 10 weeks. Bone mass, microarchitecture and strength were analyzed by dual-energy x-ray absorptiometry (DEXA), micro-CT and three-point bending test. RESULTS: Whole body bone mineral density and femoral bone mineral content significantly increased in testosterone groups (p <  0.05). Micro-CT analysis revealed that trabecular bone volume, number, separation and connectivity density were significantly improved by testosterone administration. However, the structural model index was only improved in degarelix group supplemented with 100 mg/kg EL extract (P <  0.05). The improvement of cortical thickness by EL extract was similar to that of testosterone groups (p <  0.05). Biomechanically, EL extract supplementation was able to improve stiffness, strain and modulus of elasticity in degarelix-induced groups, while stress parameter was significantly improved in orchidectomized groups (p <  0.05). CONCLUSION: Quassinoid-rich EL extract enables to protect against bone loss due to testosterone deficiency. The protective effect on cortical thickness and biomechanical parameters is comparable to testosterone group.

Insulin-like growth factor-1 is a mediator of age-related decline of bone health status in men.

OBJECTIVE: The role of insulin-like growth factor-1 (IGF-1) in bone health in men is debatable. This study aimed to determine whether IGF-1 is a mediator in age-related decline of bone health status measured by calcaneal speed of sound (SOS) in Malaysian men. METHODS: The study recruited 279 Chinese and Malay men. Their demographic data, weight, height, calcaneal SOS were taken and fasting blood was collected for total testosterone, sex-hormone binding globulin and IGF-1 assays. The associations between the studied variables were assessed using multiple linear regression (MLR) analysis. Mediator analysis was performed using Sobel test. RESULTS: There was a significant and parallel decrease of IGF-1 and SOS with age (p < 0.05). Serum IGF-1 was significantly and positively associated with SOS (p < 0.05) but after further adjustment for age, the significance was lost (p > 0.05). The strength of the association between age and SOS decreased after adjusting for IGF-1 level but it remained significant (p < 0.05). Sobel test revealed that IGF-1 was a significant partial mediator in the relationship between age and SOS (z = -4.3). CONCLUSION: Serum IGF-1 is a partial mediator in the age-related decline of bone health in men as determined by calcaneal ultrasound. A prospective study should be performed to validate this relationship.

The relationships between thyroid hormones and thyroid-stimulating hormone with lipid profile in euthyroid men.

BACKGROUND AND AIM: Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population. METHODS: A total of 708 Chinese and Malay men aged 20 years and above were recruited in this cross-sectional study. Their blood was collected for the determination of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), free thyroxine (FT4), free triiodothyronine (FT3) and TSH levels. The association was analyzed using multiple regression and logistic regression models with adjustment for age, ethnicity, body mass index and FT4/FT3/TSH levels. RESULTS: In multiple regression models, TSH was positively and significantly associated with TG (p<0.05). Free T4 was positively and significantly associated with TC, LDL-C and HDL-C (p<0.05). Free T3 was negatively and significantly associated with HDL-C (p<0.05). In binary logistic models, an increase in TSH was significantly associated with higher prevalence of elevated TG in the subjects (p<0.05), while an increase in FT4 was significantly associated with higher prevalence of elevated TC but a lower prevalence of subnormal HDL in the subjects (p<0.05). Free T3 was not associated with any lipid variables in the logistic regression (p>0.05). CONCLUSIONS: In euthyroid Malaysian men, there are positive and significant relationships between TSH level and TG level, and between FT4 level and cholesterol levels.

Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men.

BACKGROUND AND AIM: Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men. METHODS: A total of 373 men from the Malaysian Aging Male Study were included in the analysis. Data on subjects' demography, body mass index (BMI), body fat (BF) mass, waist circumference (WC), serum osteocalcin and fasting lipid levels were collected. Bioelectrical impendence (BIA) method was used to estimate BF. Multiple linear and binary logistic regression analyses were performed to analyze the association between serum osteocalcin and the aforementioned variables, with adjustment for age, ethnicity and BMI. RESULTS: Multiple regression results indicated that weight, BMI, BF mass, BF %, WC were significantly and negatively associated with serum osteocalcin (p < 0.001). There was a significant positive association between serum osteocalcin and high density lipoprotein (HDL) cholesterol (p = 0.032). Binary logistic results indicated that subjects with low serum osteocalcin level were more likely to be associated with high BMI (obese and overweight), high BF%, high WC and low HDL cholesterol (p < 0.05). Subjects with high osteocalcin level also demonstrated high total cholesterol level (p < 0.05) but this association was probably driven by high HDL level. These variables were not associated with serum C-terminal of telopeptide crosslinks in the subjects (p > 0.05). CONCLUSION: Serum osteocalcin is associated with indices of obesity and HDL level in men. These relationships should be validated by a longitudinal study, with comprehensive hormone profile testing.

Thyroid-stimulating hormone is significantly associated with bone health status in men.

BACKGROUND AND AIM: Recent studies revealed a novel association between thyroid-stimulating hormone (TSH) and bone health status in healthy male populations. The present study aimed to validate this association and provide new information on the relationship between TSH levels and calcaneal speed of sound (SOS) in men. METHODS: This cross-sectional study recruited 681 men with complete data of calcaneal SOS, body anthropometry, serum TSH, free triiodothyronine (FT3) and free thyroxine (FT4) levels. RESULTS: All subjects had FT3 and FT4 levels within the in-house reference range and 13 subjects had lower than normal TSH levels. The results revealed that the SOS value of subjects was significantly associated with TSH after multiple adjustments (p<0.05). When subjects were divided into quintiles according to their TSH levels, the difference of SOS between men with low-normal TSH and high-normal TSH contributed significantly to the association between TSH and bone health status (p<0.05). The significance of the association persisted with the inclusion and exclusion of subclinical hyperthyroid subjects. CONCLUSIONS: There was a significant association between TSH levels and bone health status in men as assessed by quantitative ultrasound. This age-independent association between TSH and SOS might explain some of the individual variation of bone health status in men.

Discrepancy between the quantitative ultrasound value of Malaysian men and the manufacturer's reference and the impact on classification of bone health status.

The local normative value in quantitative ultrasound (QUS) equipment needs to be established for wider application and accurate classification of patients into respective fracture risk groups. The present study aimed to establish the calcaneal speed of sound (SOS) value for Chinese and Malay men in Malaysia and determine the difference between calcaneal SOS of the local population and the reference values provided by the manufacturer for each age group. This study will also determine the effect of using the manufacturer's young adult (20-29yr) reference or the local young adult reference to classify the subjects into the respective risk groups. Eight hundred forty Malay and Chinese men residing in central peninsular Malaysia were recruited and their calcaneal QUS value was determined using the CM-200 machine (Furuno Electric, Nishinomiya City, Japan). The results showed that the differences in SOS values between Chinese and Malay men were not significant across all the age groups studied (p>0.05). The age-dependent reduction of SOS value assumed a biphasic form, which was evident at 30-39yr and older than 60yr. The calcaneal SOS of the subject under study was significantly higher as compared with the manufacturer's reference (based on Japanese population) in all groups aged 40yr and older (p<0.05). A significant proportion of the subjects in the osteoporosis group was misclassified using the manufacturer's young adult reference as compared with using the local young adult reference (p<0.05). In conclusion, the overall normative value of SOS obtained was suitable for Chinese and Malay men in Malaysia, and a local reference value should be applied to avoid misclassification of subjects into the respective risk groups.

Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model.

BACKGROUND: Labisia Pumila var. alata (LPva) has shown potential as an alternative to estrogen replacement therapy (ERT) in prevention of estrogen-deficient osteoporosis. In earlier studies using postmenopausal model, LPva was able to reverse the ovariectomy-induced changes in biochemical markers, bone calcium, bone histomorphometric parameters and biomechanical strength. The mechanism behind these protective effects is unclear but LPva may have regulated factors that regulate bone remodeling. The aim of this study is to determine the bone-protective mechanism of LPva by measuring the expressions of several factors involved in bone formative and resorptive activities namely Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), Macrophage-Colony Stimulating Factor (MCSF) and Bone Morphogenetic Protein-2 (BMP-2). METHODS: Thirty-two female Wistar rats were randomly divided into four groups: Sham-operated (Sham), ovariectomized control (OVXC), ovariectomized with Labisia pumila var. alata (LPva) and ovariectomized with ERT (Premarin) (ERT). The LPva and ERT were administered via daily oral gavages at doses of 17.5 mg/kg and 64.5 µg/kg, respectively. Following two months of treatment, the rats were euthanized and the gene expressions of BMP-2, OPG, RANKL and MCSF in the femoral bones were measured using a branch - DNA technique. RESULTS: The RANKL gene expression was increased while the OPG and BMP-2 gene expressions were reduced in the OVXC group compared to the SHAM group. There were no significant changes in the MCSF gene expressions among the groups. Treatment with either LPva or ERT was able to prevent these ovariectomy-induced changes in the gene expressions in ovariectomized rats with similar efficacy. CONCLUSION: LPva may protect bone against estrogen deficiency-induced changes by regulating the RANKL, OPG and BMP-2 gene expressions.

Nigella sativa: A Potential Antiosteoporotic Agent.

Nigella sativa seeds (NS) has been used traditionally for various illnesses. The most abundant and active component of NS is thymoquinone (TQ). Animal studies have shown that NS and TQ may be used for the treatment of diabetes-induced osteoporosis and for the promotion of fracture healing. The mechanism involved is unclear, but it was postulated that the antioxidative, and anti-inflammatory activities may play some roles in the treatment of osteoporosis as this bone disease has been linked to oxidative stress and inflammation. This paper highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms behind these effects and their safety profiles. NS and TQ were shown to inhibit inflammatory cytokines such as interleukin-1 and 6 and the transcription factor, nuclear factor κB. NS and TQ were found to be safe at the current dosage for supplementation in human with precautions in children and pregnant women. Both NS and TQ have shown potential as antiosteoporotic agent but more animal and clinical studies are required to further assess their antiosteoporotic efficacies.

Charcot Neuroarthropathy: Current Surgical Management and Update. A Systematic Review.

Background: Charcot neuroarthropathy of the ankle and the hindfoot is a complex clinical entity with a high risk of amputation. Charcot neuroarthropathy limb reconstruction has been proposed as a limb-salvaging procedure. However, there was a lack of information on the various available reconstruction methods, including the outcomes and complications. The present study aimed to evaluate the current literature and update on the trends regarding the surgical management of Charcot neuroarthropathy of the ankle and the hindfoot. Methods: All data published from January 2010 to January 2020 that investigated the methods of fixation and their respective outcomes for the surgical reconstruction in Charcot neuroarthropathy were analyzed. The union rate, amputation rates, and complications associated with these techniques were taken for statistical analysis. Results: A total of 16 studies fit the inclusion criteria of this study, with four Level-III studies and 12 Level-IV studies were included. Ten studies utilized internal fixation only; five used a combination of internal fixation and circular external fixator, whereby there are three comparative studies between internal and external fixations, and two studies applied combined technique of internal and external fixations (hybrid fixation). One study describes the usage of circular external fixation only. Conclusions: The use of retrograde intramedullary nail as a treatment of choice in the reconstruction of Charcot neuroarthropathy ankle is recommended before an ulcer occurrence. Hydroxyapatite (HA)- coated screws are recommended for the locking mechanism to prevent migration in Charcot neuroarthropathy due to poor bony quality. Hybrid fixation is recommended for reconstruction in a condition of ulceration and more complex deformity as it provides a higher rate of limb salvage with less soft tissue irritation.

The effects of aqueous extract of Labisia Pumila (Blume) Fern.-Vill. Var. Alata on wound contraction, hydroxyproline content and histological assessments in superficial partial thickness of second-degree burn model.

Background: Burns are considered a critical care problem in emergency medicine, resulting in physical, psychological, and chronic disabilities. Silver sulfadiazine is the gold standard in topical burn treatment but was associated with toxicity to keratinocytes and fibroblasts, which may delay wound healing. In discovering potential alternative treatments for burn wound healing, this study was performed to determine the effect of Labisia Pumila (Blume) Fern.-Vill. Var. Alata (LPVa) extract on thermal-burn wounds in rats. Methods: A total of 50 Sprague-Dawley male rats were categorized into five groups. There were three control groups; normal control (left untreated), negative control (given ointment base) and positive control (given silver sulfadiazine). Meanwhile, the two intervention groups were given with 2% LPVa leaf and root extracts, respectively. Burn wounds were inflicted on the loin region of the rat by applying a heated steel rod at 80°C for 10 s. On days 3, 7, 14, and 21, wounds were measured macroscopically using a digital calliper and one animals of each group were sacrificed, and the wounded skin were excised for histomorphological assessments. The wounds were excised for hydroxyproline content on Day 14 of treatment. Result: For wound contraction percentage, both the leaf and root extracts of LPVa showed a significant reduction in burn wound size on Day 7 onwards, when compared to other groups. For hydroxyproline content, only the leaf extract of LPVa produced significantly higher content compared to both negative and normal control groups. In terms of histological examination, the leaf extract group demonstrated a superior healing effect than the root extract group. Conclusion: Both leaf and root extracts of LPVa could promote wound healing in the thermal-burn wound rat model, with leaf extract being superior to root extract.

Underlying Familial Factors for Aggressive Behavior in Romantic Relationships: A Systematic Review.

Aggressive behavior in romantic relationship has serious effects, including both intra- and inter-personal issues. Aggressive behaviors in romantic relationships have been linked to underlying familial problems. While there have been previous reviews that studied on many interpersonal and dyadic implications of aggressive behavior in romantic relationships, there is nonetheless a lack of studies on the various components of familial factors for aggressive behavior in romantic relationships. The databases Scopus, MEDLINE, Google Scholar, and SAGE Journals were used to search for terms that are related to familial factors (family factor, family support, family relationship) as well as terms related to aggressive behavior in romantic relationships (aggression in romantic relationship, violence in intimate relationship). The articles considered for this review were original studies, samples, or subsamples of males or females who reported any underlying familial factors in childhood or adulthood that contributed to aggressive behavior in romantic relationship, and the studies must be written in English. This review has 27 papers that met the inclusion criteria. The findings from this review revealed the presence of inconsistent conclusions between familial factors and aggressive behavior in romantic relationships, with some studies failing to establish such links. These findings are reviewed with regards to the existing gaps in the literature as well as potential research options.

An insight into the anti-ulcerogenic potentials of medicinal herbs and their bioactive metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer disease (PUD) ranks top among the most prominent gastrointestinal problems prevalent around the world. Long-term use of non-steroidal anti-inflammatory drugs, pathogenic infection by Helicobacter pylori, imbalances between gastrointestinal regulatory factors and pathological hyperacidity are major contributors towards the development of peptic ulcers. Although synthetic drugs of multiple pharmacological classes are abundantly available, inadequacy of such agents in ensuring complete recovery in not uncommon. Therefore, pharmacological explorations of herbal products including plant extracts and their respective isolated phytoconstituents, for potential gastroprotective and antiulcer properties, are regular practice among the scientific community. Moreover, the historical preferences of a significant share of world population towards herbal-based medication over modern synthetic drugs also contribute significantly to such endeavors. AIM OF THE REVIEW: This review has endeavored to present ethnomedicinal and pharmacological prospects of a significant number of authenticated plant species in terms of their capacity to exert gastroprotection and antiulcer activities both in vitro and in vivo. The information delineated along the way was further subjected to critical analysis to ascertain the possible future prospects of such findings into designing plant-derived products in future for the treatment of peptic ulcer. MATERIALS AND METHODS: Electronic version of prominent bibliographic databases, including Google Scholar, PubMed, Scopus, ScienceDirect, Wiley Online Library, SpringerLink, Web of Science, and MEDLINE were explored extensively for the identification and compilation of relevant information. The plant names and respective family names were verified through the Plant List (version 1.1) and World Flora Online 2021. All relevant chemical structures were verified through PubChem and SciFinder databases and illustrated with ChemDraw Ultra 12.0. RESULTS: A colossal number of 97 plant species categorized under 58 diverse plant families have been discussed in the review for their gastroprotective and antiulcer properties. In vivo illustrations of the pharmacological properties were achieved for almost all the species under consideration. 29 individual phytoconstituents from these sources were also characterized with similar pharmacological potentials. Majority of the plant extracts as well as their constituents were found to exert their gastroprotective effects through antioxidative pathway featuring both enzymatic and nonenzymatic mechanism. Moreover, active inhibition of acid secretion, upregulation of gastroprotective mediators and downregulation of pro-inflammatory cytokines, were also associated with a prominent number of plants or products thereof. CONCLUSIONS: Comparative evaluations of the plant sources for their antiulcer activities, both as individual and as combination formulations, are necessary to be conducted in human subjects under properly regulated clinical conditions. Moreover, the efficacy and safety of such products should also be evaluated against those of the currently available treatment options. This will further facilitate in ascertaining their suitability and superiority, if any, in the treatment of peptic ulcer diseases. Implementation of these endeavors may eventually lead to development of more efficient treatment options in the future.

Antidiabetic Phytochemicals From Medicinal Plants: Prospective Candidates for New Drug Discovery and Development.

Diabetes, a chronic physiological dysfunction affecting people of different age groups and severely impairs the harmony of peoples' normal life worldwide. Despite the availability of insulin preparations and several synthetic oral antidiabetic drugs, there is a crucial need for the discovery and development of novel antidiabetic drugs because of the development of resistance and side effects of those drugs in long-term use. On the contrary, plants or herbal sources are getting popular day by day to the scientists, researchers, and pharmaceutical companies all over the world to search for potential bioactive compound(s) for the discovery and development of targeted novel antidiabetic drugs that may control diabetes with the least unwanted effects of conventional antidiabetic drugs. In this review, we have presented the prospective candidates comprised of either isolated phytochemical(s) and/or extract(s) containing bioactive phytoconstituents which have been reported in several in vitro, in vivo, and clinical studies possessing noteworthy antidiabetic potential. The mode of actions, attributed to antidiabetic activities of the reported phytochemicals and/or plant extracts have also been described to focus on the prospective phytochemicals and phytosources for further studies in the discovery and development of novel antidiabetic therapeutics.

Using primary care prescribing databases for pharmacovigilance.

AIMS: In the UK, adverse drug reactions (ADRs) are responsible for over 6.5% of all hospital admissions, representing a significant morbidity and cost burden to the health service. We aimed to develop an ADR monitoring system capable of identifying the reasons for patient discontinuation of drug therapy within 6 months of the index prescription. METHODS: Patients first prescribed amlodipine between 1 March 2004 and 28 February 2007 who discontinued their amlodipine medication within 6 months of the index prescription were identified from the practice team information (PTI) database. Once identified, reasons for amlodipine discontinuation were assessed by an electronic database search using relevant Readcodes and key words and by a direct approach to the primary care medical records. RESULTS: The PTI database identified 995 patients [61.4% females, mean age 65.9 years (SD 12.4 years)] who discontinued amlodipine within 6 months of an index prescription. An electronic search of the database, using Readcodes, identified that 19.4% (193) of patients who discontinued their medication had an ADR recorded in the database. Six (20%) of 30 participating primary care practices, contributing to the PTI database, agreed to be approached directly and supply the reasons for discontinuation for the 51 patients identified as having discontinued amlodipine in their practices. Completed data were returned for all 51 patients, 98% of whom discontinued amlodipine due to an ADR or adverse drug event. CONCLUSIONS: The results of this study confirm that primary care prescribing databases can be easily used to identify the frequency and nature of ADRs occurring in an ADR-enriched population identified through medication discontinuation.

Dengue Fever: Therapeutic Potential of Carica papaya L. Leaves.

Dengue, a very widespread mosquito-borne infectious disease caused by Aedes aegypti virus, has been occurring during the monsoons every year. The prevalence and incidence of dengue fever and death due to its complications have been increased drastically in these recent years in Bangladesh, Philippines, Thailand, Brazil, and India. Recently, dengue had spread in an epidemic form in Bangladesh, Thailand, and Philippines. Although the infection affected a large number of people around the world, there is no established specific and effective treatment by synthetic medicines. In this subcontinent, Malaysia could effectively control its incidences and death of patients using alternative medication treatment mainly prepared from Carica papaya L. leaves along with proper care and hospitalization. Papaya leaves, their juice or extract, as well as their different forms of preparation have long been used traditionally for treating dengue fever and its complications to save patients' lives. Although it is recommended by traditional healers, and the general public use Papaya leaves juice or their other preparations in dengue fever, this treatment option is strictly denied by the physicians offering treatment in hospitals in Bangladesh as they do not believe in the effectiveness of papaya leaves, thus suggesting to patients that they should not use them. In Bangladesh, 1,01,354 dengue patients have been hospitalized, with 179 deaths in the year 2019 according to information from the Institute of Epidemiology, Disease Control, and Research as well as the Directorate General of Health Services of Bangladesh. Most of the patients died because of the falling down of platelets to dangerous levels and hemorrhage or serious bleeding. Therefore, this paper aims to critically review the scientific basis and effectiveness of Carica papaya L. leaves in treating dengue fever based on preclinical and clinical reports. Thrombocytopenia is one of the major conditions that is typical in cases of dengue infection. Besides, the infection and impairment of immunity are concerned with dengue patients. This review summarizes all the scientific reports on Carica papaya L. for its ability on three aspects of dengue: antiviral activities, prevention of thrombocytopenia and improvement of immunity during dengue fever.