Cardiac hypertrophy is characteristic of heart failure in patients who have experienced cardiac remodeling. Many medicinal plants, including Parkia speciosa Hassk., have documented cardioprotective effects against such pathologies. This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsartan positive control. However, the extract did not significantly ameliorate the effects of Ang II on inducible nitric oxide synthase activity and nitric oxide levels, while valsartan did confer such protection. Although the extract decreased the levels of phosphorylated extracellular signal-related kinase, p38, and c-Jun N-terminal kinase, valsartan only decreased phosphorylated c-Jun N-terminal kinase expression. Phytochemical screening identified the flavonoids rutin (1) and quercetin (2) in the extract. These findings suggest that P. speciosa empty pod extract protects against Ang II-induced cardiomyocyte hypertrophy, possibly by modulating the Ang II/ROS/NO axis and MAPK signaling pathway via a mechanism distinct from valsartan.
The anti-allergic cromones were originally synthesized in the 1960s by Fisons Plc, and the first drug to emerge from this program, disodium cromoglycate was subsequently marketed for the treatment of asthma and other allergic conditions. Whilst early studies demonstrated that the ability of the cromones to prevent allergic reactions was due to their 'mast cell stabilizing' properties, the exact pharmacological mechanism by which this occurred, remained a mystery. Here, we briefly review the history of these drugs, recount some aspects of their pharmacology, and discuss two new explanations for their unique actions. We further suggest how these findings could be used to predict further uses for the cromones.
Bilastine is a non-sedating second generation H1 oral antihistamine (OAH) for treating allergic rhinitis (AR) patients. The effect of bilastine has not previously been evaluated in a meta-analysis. The aim of this review was to determine the efficacy and safety of bilastine in treating AR. An electronic literature search was performed using Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Science Direct and Google Scholar up to March 2021. Randomized controlled trials comparing bilastine with placebo and standard pharmacotherapy were included. The included studies must have diagnosis of AR established by clinicians and the outcomes must have a minimum of 2 weeks of follow-up period. The primary outcomes assessed were total symptom score (TSS), nasal symptom score (NSS) and non-nasal symptom score (NNSS). The secondary outcomes were discomfort due to rhinitis, quality of life (QOL) and adverse events. The risk of bias and quality of evidence for all studies were appraised. The meta-analysis was done using Review Manager 5.3 software based on the random-effects model. The search identified 135 records after removal of duplicates. Following screening and review of the records, fifteen full-text articles were assessed for eligibility. Five trials involving 3,329 patients met the inclusion criteria. Bilastine was superior to placebo in improving TSS, NSS, NNSS, rhinitis discomfort score and QOL but has comparable efficacy with other OAHs in TSS, NSS, NNS, rhinitis discomfort score and QOL. There was no difference in adverse effects when bilastine was compared against placebo and other OAHs except for somnolence. Bilastine has fewer incidence of somnolence compared to cetirizine. The overall quality of evidence ranged from moderate to high quality. Bilastine is effective and safe in treating the overall symptoms of AR with comparable efficacy and safety with other OAHs except somnolence. Whilst bilastine has similar efficacy to cetirizine, somnolence is notably less in bilastine.
Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinical and clinical studies done on some of these plants along with the possible mechanisms of action.
Andrographis paniculata (Burm. F) Nees, has been widely used for upper respiratory tract and several other diseases and general immunity for a historically long time in countries like India, China, Thailand, Japan, and Malaysia. The vegetative productivity and quality with respect to pharmaceutical properties of Andrographis paniculata varies considerably across production, ecologies, and genotypes. Thus, a field deployable instrument, which can quickly assess the quality of the plant material with minimal processing, would be of great use to the medicinal plant industry by reducing waste, and quality grading and assurance. In this paper, the potential of near infrared reflectance spectroscopy (NIR) was to estimate the major group active molecules, the andrographolides in Andrographis paniculata, from dried leaf samples and leaf methanol extracts and grade the plant samples from different sources. The calibration model was developed first on the NIR spectra obtained from the methanol extracts of the samples as a proof of concept and then the raw ground samples were estimated for gradation. To grade the samples into three classes: good, medium and poor, a model based on a machine learning algorithm - support vector machine (SVM) on NIR spectra was built. The tenfold classification results of the model had an accuracy of 83% using standard normal variate (SNV) preprocessing.
The prevalence of allergic diseases such as asthma, allergic rhinitis, food allergy and atopic dermatitis has increased dramatically in recent decades. Conventional therapies for allergy can induce undesirable effects and hence patients tend to seek alternative therapies like natural compounds. Considering the fact above, there is an urgency to discover potential medicinal plants as future candidates in the development of novel anti-allergic therapeutic agents. The Lamiaceae family, or mint family, is a diverse plant family which encompasses more than 7,000 species and with a cosmopolitan distribution. A number of species from this family has been widely employed as ethnomedicine against allergic inflammatory skin diseases and allergic asthma in traditional practices. Phytochemical analysis of the Lamiaceae family has reported the presence of flavonoids, flavones, flavanones, flavonoid glycosides, monoterpenes, diterpenes, triterpenoids, essential oil and fatty acids. Numerous investigations have highlighted the anti-allergic activities of Lamiaceae species with their active principles and crude extracts. Henceforth, this review has the ultimate aim of compiling the up-to-date (2018) findings of published scientific information about the anti-allergic activities of Lamiaceae species. In addition, the botanical features, medicinal uses, chemical constituents and toxicological studies of Lamiaceae species were also documented. The method employed for data collection in this review was mainly the exploration of the PubMed, Ovid and Scopus databases. Additional research studies were obtained from the reference lists of retrieved articles. This comprehensive summarization serves as a useful resource for a better understanding of Lamiaceae species. The anti-allergic mechanisms related to Lamiaceae species are also reviewed extensively which aids in future exploration of the anti-allergic potential of Lamiaceae species.
Ciprofloxacin, a second generation broad spectrum fluoroquinolone, is active against both Gram-positive and Gram-negative bacteria. Ciprofloxacin has a high oral bioavailability and a large volume of distribution. It is used for the treatment of a wide range of infections including urinary tract infections caused by susceptible bacteria. However, the availability and use of substandard and spurious quality of oral ciprofloxacin formulations in the developing countries has been thought to have contributed toward increased risk of treatment failure and bacterial resistance. Therefore, quality control and bioequivalence studies of the commercially available oral ciprofloxacin formulations should be monitored. Appropriate actions should be taken against offending manufacturers in order to prevent the sale of substandard and spurious quality of ciprofloxacin formulations.
Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties.Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone (1), 3,3',4',5',5,6,7,8-octamethoxyflavone (exoticin) (2), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone (3), and 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone (4), isolated and identified fromN. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds1,3, and4(12.5-25 mg/kg b.w.) exhibited dose-dependent and significant (p< 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K+channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound1,3, and4(12.5 mg/kg b.w.) demonstrated significant (p< 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAAreceptor in the action of compound3and4was evident from the reversal effects of flumazenil. In addition, compounds1and4(12.5-25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1-4) fromN. Plumbaginifoliacould be considered as suitable candidates for the development of analgesic and anxiolytic agents.
Epilepsy is a severe neurological disorder involving 70 million people around the globe. Epilepsy-related neuropsychiatric comorbidities such as depression, which is the most common, is an additional factor that negatively impacts the living quality of epilepsy patients. There are many theories and complexities associated with both epilepsy and associated comorbidities, one of which is the gut-brain-axis influence. The gut microbiome is hypothesized to be linked with many neurological disorders; however, little conclusive evidence is available in this area. Thus, highlighting the role will create interest in researchers to conduct detailed research in comprehending the influence of gut-brain-axis in the manifestation of depressive symptoms in epilepsy. The hypothesis which is explored in this review is that the gut-brain-axis do play an important role in the genesis of epilepsy and associated depression. The correction of this dysbiosis might be beneficial in treating both epilepsy and related depression. This hypothesis is illustrated through extensive literature discussion, proposed experimental models, and its applicability in the field. There is indirect evidence which revealed some specific bacterial strains that might cause depression in epilepsy.
Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.
Background. Infertility is an emerging health issue for men. Comparative efficacy of different pharmacological interventions on male infertility is not clear. The aim of this review is to investigate the efficacy of various pharmacological interventions among men with idiopathic male infertility. All randomized control trials evaluating the effectuality of interventions on male infertility were included for network meta-analysis (NMA) from inception to 31 April 2020, systematically performed using STATA through the random effect model. The protocol was registered at PROSPERO (CRD42020152891). Results. The outcomes of interest were semen and hormonal parameters. Treatment effects (p < 0.05) were estimated through WMD at the confidence interval of 95%. Upon applying exclusion criteria, n=28 RCTs were found eligible for NMA. Results from NMA indicated that consumption of supplements increases sperm concentration levels [6.26, 95% CI 3.32, 9.21] in comparison to SERMs [4.97, 95% CI 1.61, 8.32], hormones [4.14, 95% CI 1.83, 6.46], and vitamins [0.15, 95% CI -20.86, 21.15)] with placebo, whereas the use of SERMs increased percentage sperm motility [6.69, 95% CI 2.38, 10.99] in comparison to supplements [6.46, 95% CI 2.57, 10.06], hormones [3.47, 95% CI 0.40, 6.54], and vitamins [-1.24, 95% CI -11.84, 9.43] with placebo. Consumption of hormones increased the sperm morphology [3.71, 95% CI, 1.34, 6.07] in contrast to supplements [2.22, 95% CI 0.12, 4.55], SERMs [2.21, 95% CI -0.78, 5.20], and vitamins [0.51, 95% CI -3.60, 4.62] with placebo. Supplements boosted the total testosterone levels [2.70, 95% CI 1.34, 4.07] in comparison to SERMs [1.83, 95% CI 1.16, 2.50], hormones [0.40, 95% CI -0.49, 1.29], and vitamins [-0.70, 95% CI -6.71, 5.31] with placebo. SERMs increase the serum FSH levels [3.63, 95% CI 1.48, 5.79] better than hormones [1.29, 95% CI -0.79, 3.36], vitamins [0.03, 95% CI -2.69, 2.76], and supplements [-4.45, 95% CI -7.15, -1.76] in comparison with placebo. Conclusion. This review establishes that all interventions had a significantly positive effect on male infertility. Statistically significant increased sperm parameters were noted in combinations of zinc sulfate (220 mg BID), clomiphene citrate (50 mg BID), and testosterone undecanoate and CoQ10; tamoxifen citrate and FSH were shown to improve the hormonal profile in infertile males.
Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein's anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 μg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.
Background: Countries across Africa and Asia have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE). However, there has been considerable controversy surrounding some treatments including hydroxychloroquine where the initial hype and misinformation led to shortages, price rises and suicides. Price rises and shortages were also seen for PPE. Such activities can have catastrophic consequences especially in countries with high co-payment levels. Consequently, there is a need to investigate this further. Objective: Assess changes in utilisation, prices, and shortages of pertinent medicines and PPE among African and Asian countries since the start of pandemic. Our approach: Data gathering among community pharmacists to assess changes in patterns from the beginning of March until principally the end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: One hundred and thirty one pharmacists took part building on the earlier studies across Asia. There were increases in the utilisation of principally antimalarials (hydroxychloroquine) and antibiotics (azithromycin) especially in Nigeria and Ghana. There were limited changes in Namibia and Vietnam reflecting current initiatives to reduce inappropriate prescribing and dispensing of antimicrobials. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries where documented. In addition, generally limited change in the utilisation of herbal medicines. However, shortages have resulted in appreciable price increases in some countries although moderated in others through government initiatives. Suggestions in Namibia going forward included better planning and educating patients. Conclusion: Encouraging to see increases in the utilisation of vitamins/immune boosters and PPE. However, concerns with increased utilisation of antimicrobials needs addressing alongside misinformation, unintended consequences from the pandemic and any appreciable price rises. Community pharmacists and patient organisations can play key roles in providing evidence-based advice, helping moderate prices through improved stock management, and helping address unintended consequences of the pandemic.
Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.
Musculoskeletal health is paramount in an ageing population susceptible to conditions such as osteoporosis, arthritis and fractures. Age-related changes in bone, muscle, and joint function result in declining musculoskeletal health, reduced mobility, increased risk of falls, and persistent discomfort. Preserving musculoskeletal wellbeing is essential for maintaining independence and enhancing the overall quality of life for the elderly. The global burden of musculoskeletal disorders is significant, impacting 1.71 billion individuals worldwide, with age-related muscle atrophy being a well-established phenomenon. Tocotrienols, a unique type of vitamin E found in various sources, demonstrate exceptional antioxidant capabilities compared to tocopherols. This characteristic positions them as promising candidates for addressing musculoskeletal challenges, particularly in mitigating inflammation and oxidative stress underlying musculoskeletal disorders. This review paper comprehensively examines existing research into the preventive and therapeutic potential of tocotrienols in addressing age-related musculoskeletal issues. It sheds light on the promising role of tocotrienols in enhancing musculoskeletal health and overall wellbeing, emphasizing their significance within the broader context of age-related health concerns.
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.
The aim of this study was to evaluate the cytotoxic potential of a novel nickel(II) complex (NTC) against WiDr and HT-29 human colon cancer cells by determining the IC50 using the standard MTT assay. The NTC displayed a strong suppressive effect on colon cancer cells with an IC50 value of 6.07 ± 0.22 μM and 6.26 ± 0.13 μM against WiDr and HT-29 respectively, after 24 h of treatment. Substantial reduction in the mitochondrial membrane potential and increase in the release of cytochrome c from the mitochondria directed the induction of the intrinsic apoptosis pathway by the NTC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. The NTC was also shown to activate the extrinsic pathway of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of the current work indicates that NTC possess a potent cancer cell abolishing activity by simultaneous induction of intrinsic and extrinsic pathways of apoptosis in colon cancer cell lines.
Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa. The pharmacological studies reported in vitro, in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N. sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.