Appetite Suppressing Activity of Rumex Usambarensis Leaf and Stem Aqueous Extract in Wistar Albino Female Rats: an in vivo Experimental Study.

Background: The burden of obesity and overweight associated morbidity and mortality is increasing in epidemic proportions worldwide. Suppression of appetite is one of the mechanisms that has been shown to reduce weight. Most of the drugs on the market currently for appetite suppression are not readily available or affordable in resource-limited settings. Additionally, previous studies have shown that most of these drugs are associated with significant adverse effects, which demonstrates a need for alternative or complementary options of drugs for appetite suppression. In Uganda, herdsmen commonly chew the raw stems and leaves of Rumex usambarensis, a wild shrub, and this is believed to reduce hunger. This study aimed at determining the effect of Rumex usambarensis aqueous extract on food intake as a measure of appetite in Wistar albino rats. Methods: This study was carried out in two phases: the fattening phase and the treatment phase. Female albino Wistar rats were fed a high-fat diet for 49 days. The fattened animals were then randomly separated into 4 groups, which received 1 mL of distilled water (negative control), 500 mg/kg body weight of aqueous extract of Rumex usambarensis, 1000 mg/kg body weight of the extract and 20 mg/kg body weight topiramate (positive control), respectively. Food intake was measured every day, and weights were taken every two days for every group. Results: Rumex usambarensis extract significantly reduced body weight of fattened rats compared to the control group at both doses: for the 500mg/kg dose (Mean difference, MD = 17.2, p < 0.001) and for 1000mg/kg dose (MD = 25.9, p < 0.001). Additionally, both doses of the aqueous extract showed a significant reduction in food intake: for the 500mg/kg dose (MD = 16.1, p < 0.001) and for the 1000mg/kg dose (MD = 37.3, p < 0.001). There was a strong correlation between food intake and weight for both doses for the 500mg/kg dose (r = 0.744, p = 0.009), and the strongest association observed with 1000mg/kg dose (r = 0.906, p < 0.001). Conclusion: The aqueous extract of the leaves and stems of Rumex usambarensis has appetite suppressing and weight reduction effects in fattened female Wistar albino rats and could be an efficacious alternative medicine for management of overweight, obesity and other related disorders.

Chemometric Classification of Mangifera indica L. Leaf Cultivars, Based on Selected Phytochemical Parameters; Implications for Standardization of the Pharmaceutical Raw Materials.

Introduction: Mangifera indica leaves are among the most common materials employed in manufacturing herbal medicinal products. Despite the phytochemical variation of M. indica cultivars, there are no monographs to guide the cultivation, processing, and authentication of the materials. Methods: This study characterized 15 Ugandan M. indica leaf varieties, with reference to extraction index (EI), total phenolic content (TPC), antioxidant activity (AOA), and mangiferin concentration (MC). In addition, HPLC fingerprints were established to evaluate the overall phytoequivalence of the materials. Then, using hierarchical clustering (HC) and principal component analysis (PCA), the materials were assigned quality grades. Results: The mean EI was 9.39 ± 1.64% and varied among the varieties (P=0.001); the TPC varied significantly (P < 0.0001), from 183.29 ± 2.36 mg/g (Takataka) to 79.47 ± 0.58 mg/g (Apple mango). AOA ranged from 16.81 ± 2.85 µg/mL (Doodo red) to 87.85 µg/mL (Asante). MC varied significantly (P < 0.0001), from 105.75 ± 0.60 mg/g (Kate) to 39.53 ± 0.30 mg/g (Asante). HC gave four major grades: A to D (A, varieties with the highest TPC, MC, and AOA). These parameters reduced to below average from group B to group D. The chromatographic fingerprints were visually similar, but the number of peaks varied, from 19 (Kawanda green) to 29 (Kawanda wide), with 23.5 ± 2.9 average peaks. Whole fingerprints were less similar (r < 0.8) than common peak fingerprints (r > 0.9, P < 0.001). PCA grouped the fingerprints into five clusters; loading plots for PC 1 and 2 revealed two important compounds, one at Rt = 15.828 minutes (mangiferin) and the other at 6.021 minutes. Using the standardized common fingerprints, unknown field samples clustered closely with Koona, Kate, and Kawanda green varieties. Conclusions: The EI, TPC, MC, and AOA values can be utilized to monitor consistency in the quality of materials and the production process. The grades generated can be used to select materials for cultivation and manufacturing. Where minimum concentrations are set, materials of different concentrations are used to dilute or concentrate each other. The HPLC fingerprints can be utilized to authenticate the materials. More samples from different agroecological regions of the country should be tested to cater to climatic variations in order to develop GMP-compliant botanical identification methods.

Safety and Efficacy of Medicinal Plants Used to Manufacture Herbal Products with Regulatory Approval in Uganda: A Cross-Sectional Study.

Introduction: The Uganda National Drug Authority requires phytochemical screening, freedom from microbial contamination, and evidence of safety and efficacy of the constituent plants to register herbal products. Since Uganda has no pharmacopeia, safety, efficacy, and plant processing information are not readily available. We documented the plant materials used to manufacture products in Uganda and established evidence of their safety and efficacy and availability of monographs. Methods: The NDA register of herbal products was reviewed, and a product list was extracted. The herbal products were purchased from local pharmacies, and their labels were studied to identify plant ingredients and drug use. Literature was reviewed to document evidence of the safety and efficacy of the plant materials concerning manufacturer's claims. Also, the WHO and available African Pharmacopeia were searched to establish the availability of the plant monographs. Results: Of the 84 NDA-registered local products, only 18 were obtained from the market; 82% were indicated for respiratory tract disorders. Thirty-three plant materials were listed with Eucalyptus globulus Labill, being the commonest. Several in vitro and in vivo studies demonstrate efficacy, thus supporting the use of the selected plant species for empirical treatment as stated on the product label. While most plants were safe, some species such as Albizia coriaria Oliv. had dose-dependent toxicities that cannot be predicted in combinations. The WHO, African Pharmacopoeia, and West African Herbal Pharmacopoeia had only 16 plant monographs of the 33 plants of interest. Nevertheless, Aloe vera (L.) Burm.f., Azadirachta indica A.Juss., Zingiber officinale Roscoe, and Allium sativum L. monographs were published by all three pharmacopoeias. Conclusions: Preclinical evidence of safety and efficacy exists in the literature for most of the plants used to manufacture registered herbal products in Uganda. More specific bioassays and clinical trials are required for the products to provide conclusive evidence of safety and toxicity. Monographs are urgently needed for the Ugandan plants.

Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats.

BACKGROUND: Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. METHODS: Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals' relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. RESULTS: There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats' relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium's inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. CONCLUSION: The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.

Antidiabetic Medicinal Plants Used in Democratic Republic of Congo: A Critical Review of Ethnopharmacology and Bioactivity Data.

Several studies have been conducted and published on medicinal plants used to manage Diabetes Mellitus worldwide. It is of great interest to review available studies from a country or a region to resort to similarities/discrepancies and data quality. Here, we examined data related to ethnopharmacology and bioactivity of antidiabetic plants used in the Democratic Republic of Congo. Data were extracted from Google Scholar, Medline/PubMed, Scopus, ScienceDirect, the Wiley Online Library, Web of Science, and other documents focusing on ethnopharmacology, pharmacology, and phytochemistry antidiabetic plants used in the Democratic Republic of Congo from 2005 to September 2021. The Kew Botanic Royal Garden and Plants of the World Online web databases were consulted to verify the taxonomic information. CAMARADES checklist was used to assess the quality of animal studies and Jadad scores for clinical trials. In total, 213 plant species belonging to 72 botanical families were reported. Only one plant, Droogmansia munamensis, is typically native to the DRC flora; 117 species are growing in the DRC and neighboring countries; 31 species are either introduced from other regions, and 64 are not specified. Alongside the treatment of Diabetes, about 78.13% of plants have multiple therapeutic uses, depending on the study sites. Experimental studies explored the antidiabetic activity of 133 plants, mainly in mice, rats, guinea pigs, and rabbits. Several chemical classes of antidiabetic compounds isolated from 67 plant species have been documented. Rare phase II clinical trials have been conducted. Critical issues included poor quality methodological protocols, author name incorrectly written (16.16%) or absent (14.25%) or confused with a synonym (4.69%), family name revised (17.26%) or missing (1.10%), voucher number not available 336(92.05%), ecological information not reported (49.59%). Most plant species have been identified and authenticated (89.32%). Hundreds of plants are used to treat Diabetes by traditional healers in DRC. However, most plants are not exclusively native to the local flora and have multiple therapeutic uses. The analysis showed the scarcity or absence of high-quality, in-depth pharmacological studies. There is a need to conduct further studies of locally specific species to fill the gap before their introduction into the national pharmacopeia.

Prevalence, characteristics and predicting risk factors of adverse drug reactions among hospitalized older adults: A systematic review and meta-analysis.

BACKGROUND: Occurrence of adverse drug reactions is a major global health problem mostly affecting older adults. Identifying the magnitude and predictors of adverse drug reactions is crucial to developing strategies to mitigate the burden of adverse drug reactions. This study's objectives were to estimate and compare the prevalences of adverse drug reactions, to characterize them and to identify the predictors among hospitalized older adults. METHODS: A comprehensive systematic literature search including both prevalence and risk factors of adverse drug reactions in hospitalized older adults was conducted using PubMed, Scopus and Google Scholar, involving all articles published in English. Descriptive statistics and comparison of means was performed using SPSS version 20.0 and metaprop command was performed in STATA version 13.0. Heterogeneity was assessed using I 2 statistic. RESULTS: A total of 18 studies, involving 80,695 participants with a median age of 77 years, were included in this study. The pooled prevalence of adverse drug reaction was 22% (95% confidence interval: 17%, 28%; I 2 = 99.23%). Among high-income countries, the prevalence of adverse drug reactions was 29% (95% confidence interval: 16%, 42%) as compared to 19% (95% confidence interval: 14%-25%) in low and middle-income countries (p value = 0.176). Of the 620 adverse drug reactions categorized, most were type A (89%), which are generally predictable and preventable. Two-thirds (795, 67%) of the adverse drug reactions were probable and most (1194, 69%) were mild or moderate. The majority (60%) of the categorized adverse drug reactions were preventable and less than one-third (31%) were severe. The most consistently reported predictors of adverse drug reactions in hospitalized older patients were medication-related factors, including polypharmacy and potentially inappropriate medications followed by disease-related factors-renal failure, complex comorbidity, heart failure and liver failure. CONCLUSION: Almost one-quarter of all hospitalized older adults experienced at least one adverse drug reaction during their hospital stay. The majority of the adverse drug reactions were preventable. Medication-related factors were the most consistently reported predictors of adverse drug reactions followed by disease-related factors.

Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox.

BACKGROUND: Aloe vera and Aloe ferox have over the years been among the most sought-after Aloe species in the treatment of ailments worldwide. This review provides categorized literature on the phytochemical and scientifically proven toxicological profiles of A. vera and A. ferox to facilitate their exploitation in therapy. MAIN BODY OF THE ABSTRACT: Original full-text research articles were searched in PubMed, ScienceDirect, Research gate, Google Scholar, and Wiley Online Library using specific phrases. Phenolic acids, flavonoids, tannins, and anthraquinones were the main phytochemical classes present in all the two Aloe species. Most of the phytochemical investigations and toxicity studies have been done on the leaves. Aloe vera and Aloe ferox contain unique phytoconstituents including anthraquinones, flavonoids, tannins, sterols, alkaloids, and volatile oils. Aloe vera hydroalcoholic leaf extract showed a toxic effect on Kabir chicks at the highest doses. The methanolic, aqueous, and supercritical carbon dioxide extracts of A. vera leaf gel were associated with no toxic effects. The aqueous leaf extract of A. ferox is well tolerated for short-term management of ailments but long-term administration may be associated with organ toxicity. Long-term administration of the preparations from A. vera leaves and roots was associated with toxic effects. SHORT CONCLUSION: This review provides beneficial information about the phytochemistry and toxicity of A. vera and A. ferox and their potential in the treatment of COVID-19 which up to date has no definite cure. Clinical trials need to be carried out to clearly understand the toxic effects of these species.

Developmental stages influence in vivo antimalarial activity of aerial part extracts of Schkuhria pinnata.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria remains a dire health challenge, particularly in sub-Saharan Africa. In Uganda, it is the most ordinary condition in hospital admission and outpatient care. The country's meager health services compel malaria patients to use herbal remedies such as Schkuhria pinnata (Lam.) Kuntze ex Thell (Asteraceae). Although in vivo studies tested the antimalarial activity of S. pinnata extracts, plant developmental stages and their effect at different doses remain unknown. AIM OF THE STUDY: This study aims to determine the effect of the plant developmental stage on the antimalarial activity of S. pinnata in mice and to document the acute oral toxicity profile. METHODS: Seeds of S. pinnata were grown, and aerial parts of each developmental stage were harvested. Extraction was done by maceration in 70% methanol. The antimalarial activity was evaluated using chloroquine-sensitive Plasmodium berghei on swiss albino mice, in a chemosuppressive test, at 150, 350, and 700 mg/kg, p.o. Standard drugs used were artemether-lumefantrine (0.57 + 3.43) mg/kg and chloroquine (10 mg/kg) as positive controls. Distilled water at 1 mL/100g was used as a negative control. The Lorke method was adopted to determine the acute toxicity of extracts. RESULTS: The flowering stage extract had a maximum suppression of parasitemia at 700 mg/kg (68.83 ± 4.49%). Extract at other developmental stages also significantly suppressed the parasitemia (in the ascending order) fruiting (50.71 ± 1.87%), budding (54.92 ± 7.56%), vegetative (55.39 ± 2.01%) compared to the negative control (24.7 ± 2.7%), p < 0.05. Extracts from all developmental stages increased survival time, with the flowering stage having the highest survival time at 20.33 ± 0.88 days. All extracts had an LD50 of 2157 mg/kg, implying that extracts are safe at lower doses. CONCLUSION: Together, our findings revealed that the S. pinnata extracts at the flowering stage had superior antimalarial activity compared to other plant developmental stages. Extracts from all developmental stages have demonstrated a dose-dependent suppression of malarial parasites and increased survival time with an LD50 of 2157 mg/kg. Thus, for better antimalarial activity, local communities could consider harvesting S. pinnata at the flowering stage. Further studies are needed to isolate pure compounds from S. pinnata and determine their antimalarial activity.

Ethno medical knowledge and traditional use of Aristolochia bracteolata Lam. for malaria among local communities in Jubek State of South Sudan: A cross-sectional survey.

ETHNOPHARMACOLOGICAL RELEVANCE: The recognized challenges to access conventional antimalarial medicines could have contributed to the extensive use of Aristolochia bracteolata Lam. (Aristolochiaceae)to manage malaria in South Sudan traditionally. However, the use and acquired experiences are notwell documented. AIM OF THE STUDY: This study aimed to document the traditional use of A. bracteolata for malaria treatment and experiences among the local communities in Jubek State of South Sudan. METHODS: We performed a cross-sectional study in four counties in Jubek State and interviewed 396 community members, including traditional healers, using a semi-structured questionnaire. Four focused group discussions (FGDs) were also conducted using the interviewer guide. The inclusion criteria were; adults 18 years and older, men andwomen participants, at least one year residing in the study area before the study, and those with a history of medicinal plant use. Data were summarized and presented as proportions. Qualitative data were analyzed using a thematic content approach. The major themes that emerged were discussed. We applied the Pearson Chi-Square test at α = 0.05 to test the study's significant differences in responses. The statistical package for social sciences version 21 software was used for data analysis. RESULTS: Women accounted for 208 (52.5%) of participants, with the majority 321 (81.1%) were between 18 and 45 years. Interestingly, most 312 (78.8%) had formal education. Moreover, about 208 (52.5%) participants collect the plant in their vicinity, where leaves were the most commonly used part 277 (46.4%), followed by the roots, seeds, and stems at 245(41.0%), 71 (11.9%), and 4 (0.7%), respectively. Furthermore, about 63 (15.9%) of the participants experienced side effects, including early abortions, heartburns, sweating, and stomach discomforts. Conversely, a total of 387 (96.0%) reported getting cured of malaria. Generally, the quantity of medicine taken per day differs concerning parts of the plant, with leaves ranging from 1 to 10 pieces, roots at 0.4-1 g, and seeds at 0.1-0.5 g. The locals used these plant parts to prepare infusion and decoction traditional dosage forms for oral use. CONCLUSION: The documented medicinal plant's therapeutic uses provided critical information on the traditional use of A. bracteolata by the community in Jubek state of South Sudan to treat malaria. Although most users reported getting cured of malaria, a notable proportion of them experienced side effects, including early-stage abortion and stomach discomforts. Thus, the use of A. bracteolata preparations, particularly in pregnant women, should be avoided. Finally, further studies are needed to devise a strategy to neutralize the toxic compounds and create community awareness on best practices to minimize side effects.

Potential Benefits of Antiviral African Medicinal Plants in the Management of Viral Infections: Systematic Review.

Background: Viruses cause various human diseases, some of which become pandemic outbreaks. This study synthesized evidence on antiviral medicinal plants in Africa which could potentially be further studied for viral infections including Coronavirus disease 2019 (COVID-19) treatment. Methods: PUBMED, CINAHIL, Scopus, Google Scholar, and Google databases were searched through keywords; antiviral, plant, herb, and Africa were combined using "AND" and "OR". In-vitro studies, in-vivo studies, or clinical trials on botanical medicine used for the treatment of viruses in Africa were included. Results: Thirty-six studies were included in the evidence synthesis. Three hundred and twenty-eight plants were screened for antiviral activities of which 127 showed noteworthy activities against 25 viral species. These, were Poliovirus (42 plants), HSV (34 plants), Coxsackievirus (16 plants), Rhinovirus (14plants), Influenza (12 plants), Astrovirus (11 plants), SARS-CoV-2 (10 plants), HIV (10 plants), Echovirus (8 plants), Parvovirus (6 plants), Semiliki forest virus (5 plants), Measles virus (5 plants), Hepatitis virus (3 plants), Canine distemper virus (3 plants), Zika virus (2 plants), Vesicular stomatitis virus T2 (2 plants). Feline herpesvirus (FHV-1), Enterovirus, Dengue virus, Ebola virus, Chikungunya virus, Yellow fever virus, Respiratory syncytial virus, Rift Valley fever virus, Human cytomegalovirus each showed sensitivities to one plant. Conclusion: The current study provided a list of African medicinal plants which demonstrated antiviral activities and could potentially be candidates for COVID-19 treatment. However, all studies were preliminary and in vitro screening. Further in vivo studies are required for plant-based management of viral diseases.

Identification of Antimicrobial Peptides Isolated From the Skin Mucus of African Catfish, Clarias gariepinus (Burchell, 1822).

Antimicrobial peptides (AMPs) constitute a broad range of bioactive compounds in diverse organisms, including fish. They are effector molecules for the innate immune response, against pathogens, tissue damage and infections. Still, AMPs from African Catfish, Clarias gariepinus, skin mucus are largely unexplored despite their possible therapeutic role in combating antimicrobial resistance. In this study, African Catfish Antimicrobial peptides (ACAPs) were identified from the skin mucus of African Catfish, C. gariepinus. Native peptides were extracted from fish mucus scrapings in 10% acetic acid (v/v) and ultra-filtered using 5 kDa molecular weight cut-off membrane. The extract was purified using C18 Solid-Phase Extraction. The antibacterial activity was determined using the Agar Well Diffusion method and broth-dilution method utilizing Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922). Thereafter, Sephadex G-25 gel filtration was further utilized in bio-guided isolation of the most active fractions prior to peptide identification using Orbitrap Fusion Lumos Tribrid Mass Spectrometry. The skin mucus extracted from African Catfish from all the three major lakes of Uganda exhibited antimicrobial activity on E. coli and S. aureus. Lake Albert's C. gariepinus demonstrated the best activity with the lowest MIC of 2.84 and 0.71 µg/ml on S. aureus and E. coli, respectively. Sephadex G-25 peak I mass spectrometry analysis (Data are available via ProteomeXchange with identifier PXD029193) alongside in silico analysis revealed seven short peptides (11-16 amino acid residues) of high antimicrobial scores (0.561-0.905 units). In addition, these peptides had a low molecular weight (1005.57-1622.05 Da) and had percentage hydrophobicity above 54%. Up to four of these AMPs demonstrated α-helix structure conformation, rendering them amphipathic. The findings of this study indicate that novel AMPs can be sourced from the skin mucus of C. gariepinus. Such AMPs are potential alternatives to the traditional antibiotics and can be of great application to food and pharmaceutical industries; however, further studies are still needed to establish their drug-likeness and safety profiles.

The safety and efficacy of Momordica charantia L. in animal models of type 2 diabetes mellitus: A systematic review and meta-analysis.

Type 2 diabetes mellitus is a chronic hyperglycemic condition due to progressively impaired glucose regulation. Momordica charantia L. could potentially improve hyperglycemia because its fruit extracts can alleviate insulin resistance, beta-cell dysfunction, and increase serum insulin level. We evaluated the effect of M. charantia L. in comparison with a vehicle on glycemic control in animal models of type 2 diabetes mellitus. MEDLINE, Web of Science, Scopus, and CINAHL databases were searched without language restriction through April 2019. About 66 studies involving 1861 animals that examined the effect of M. charantia L. on type 2 diabetes mellitus were included. Fruits and seed extracts reduced fasting plasma glucose (FPG) and glycosylated hemoglobin A1c in comparison to vehicle control: (42 studies, 815 animals; SMD, -6.86 [95% CI; -7.95, -5.77], 3 studies, 59 animals; SMD; -7.76 [95% CI; -12.50, -3.01]) respectively. Also, the extracts have hepato-renal protective effects at varying doses and duration of administration. Despite the observed significant glycemic control effect, poor methodological quality calls for future researches to focus on standardizing extract based on chemical markers and adopt measures to improve the quality of preclinical studies such as sample size calculation, randomization, and blinding.

New Putative Antimicrobial Candidates: In silico Design of Fish-Derived Antibacterial Peptide-Motifs.

Antimicrobial resistance remains a great threat to global health. In response to the World Health Organizations' global call for action, nature has been explored for novel and safe antimicrobial candidates. To date, fish have gained recognition as potential source of safe, broad spectrum and effective antimicrobial therapeutics. The use of computational methods to design antimicrobial candidates of industrial application has however, been lagging behind. To fill the gap and contribute to the current fish-derived antimicrobial peptide repertoire, this study used Support Vector Machines algorithm to fish out fish-antimicrobial peptide-motif candidates encrypted in 127 peptides submitted at the Antimicrobial Peptide Database (APD3), steered by their physico-chemical characteristics (i.e., positive net charge, hydrophobicity, stability, molecular weight and sequence length). The best two novel antimicrobial peptide-motifs (A15_B, A15_E) with the lowest instability index (-28.25, -22.49, respectively) and highest isoelectric point (pI) index (10.48 for each) were selected for further analysis. Their 3D structures were predicted using I-TASSER and PEP-FOLD servers while ProSA, PROCHECK, and ANOLEA were used to validate them. The models predicted by I-TASSER were found to be better than those predicted by PEP-FOLD upon validation. Two I-TASSER models with the lowest c-score of -0.10 and -0.30 for A15_B and A15_E peptide-motifs, respectively, were selected for docking against known bacterial-antimicrobial target-proteins retrieved from protein databank (PDB). Carbapenam-3-carboxylate synthase (PDB ID; 4oj8) yielded the lowest docking energy (-8.80 and -7.80 Kcal/mol) against motif A15_B and A15_E, respectively, using AutoDock VINA. Further, in addition to Carbapenam-3-carboxylate synthase, these peptides (A15_B and A15_E) were found to as well bind to membrane protein (PDB ID: 1by3) and Carbapenem synthetase (PDB: 1q15) when ClusPro and HPEPDOCK tools were used. The membrane protein yielded docking energy scores (DES): -290.094, -270.751; coefficient weight (CW): -763.6, 763.3 for A15_B and A15_E) whereas, Carbapenem synthetase (PDB: 1q15) had a DES of -236.802, -262.75 and a CW of -819.7, -829.7 for peptides A15_B and A15_E, respectively. Motif A15_B of amino acid positions 2-19 in Pleurocidin exhibited the strongest in silico antimicrobial potentials. This segment could be a good biological candidate of great application in pharmaceutical industries as an antimicrobial drug candidate.

Three promising antimycobacterial medicinal plants reviewed as potential sources of drug hit candidates against multidrug-resistant tuberculosis.

Regimens of current drugs for tuberculosis are lengthy and are associated with many adverse effects. Currently, the emergence of different resistant strains has been observed. This urges a need for the discovery and development of novel drugs. The main sources of drug lead candidates are based on natural products. Zanthoxylum leprieurii, Lantana camara, and Cryptolepis Sanguinolenta are among the plants that have antimycobacterial activity. Recent technological methods, such as metabolomics, can rapidly detect and identify active compounds from medicinal plants. In this review, we aim to provide an overview and discussion of the antimycobacterial activity, phytochemical analysis and toxicity profile of these plants and their products as well as the potential of metabolomic fingerprinting of medicinal plants with a given activity on microbes, in the search for the potential drug hit molecules. The information for this review was extracted from databases such as Excerpta Medica Database, Google Scholar, Springer, and PubMed Central. Primary studies, using a combination of the keywords antimycobacterial medicinal plant, multidrug-resistant tuberculosis, phytochemistry, toxicity, Zanthoxylum leprieurii, Lantana camara, Cryptolepis sanguinolenta, and plant metabolomics/metabolic fingerprinting of plant extracts, have been considered. The above-mentioned plant species showed antimycobacterial activity against drug-resistant strains of M. tuberculosis. They may provide potential candidates for novel drugs against multidrug-resistant tuberculosis. However, extensive work is still needed. To our knowledge, there is no or limited literature that reports the metabolic fingerprints of these plants. The analysis of the metabolite fingerprints of medicinal plants with similar antimicrobial activity could be important to determine whether the activity results from common metabolites within different plant species. This review shows that these plants are potential candidates to provide drug hits against multidrug-resistant tuberculosis strains. Future studies of compound optimization, in vivo safety and efficacy, as well as of the specific mechanisms of action are however required.

Pharmacology, Phytochemistry, and Toxicity Profiles of Phytolacca dodecandra L'Hér: A Scoping Review.

INTRODUCTION: Phytolacca dodecandra L'Hér. is a native plant of sub-Saharan Africa and Madagascar which is traditionally used for various ailments. Concerned with the scope of the available evidence, we designed a scoping review to critically analyze scientific evidence on P dodecandra's pharmacology, toxicity, and phytochemistry to validate its ethnomedical use. METHODS: We searched without language restriction in MEDLINE, Google Scholar, Scopus, Embase, and Web of Science through December 2019. Both published and unpublished articles were assessed for relevance and reviewed. RESULTS: Of 600 articles retrieved through database search, a total of 48 articles were finally included. The butanol extract of berries was more potent molluscicidal than aqueous extract. The berries had also miracidial, anthelmintic, antifungal activity, and antibacterial effect against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella spp. The methanol extracts of roots had an antifungal effect against Candida albicans, Cryptococcus neoformans, Microsporum gypseum, and Trichophyton mentagrophytes. Phytolacca dodecandra was toxic to aquatic invertebrate and fish. The fishes were up to 4 times more sensitive than snails. Saponins were the main phytoconstituent isolated from berries. Terpenoid and phenolic were abundant in leaves and bark extracts. CONCLUSIONS: Studies validated the traditional use of P dodecandra against snails, worms, and various bacterial and fungal infections. Limited phytochemical data call for future research to focus on isolation of compounds; test their toxicity and activity; and establish mechanism of action.

Efficacy and safety of cinnamon in type 2 diabetes mellitus and pre-diabetes patients: A meta-analysis and meta-regression.

INTRODUCTION: Cinnamon has been used as a dietary component and in the management of diabetes mellitus. This study systematically reviewed and synthesized evidence on the efficacy of cinnamon for the treatment of type 2 diabetes mellitus (T2DM) and pre-diabetes patients. METHODS: Databases of Web of Sciences, the Cochrane library, PubMed, CINAHL and SCOPUS were searched. Stata version 13 (College Station, Texas 77845 USA) and RevMan var. 5.3 software were used for meta-analysis. Heterogeneity was assessed using Chi-square and I2 tests. RESULTS: Sixteen randomized controlled studies were included in the meta-analysis. Cinnamon significantly reduced fasting blood glucose (FBG) and homeostatic model assessment for insulin resistance (HOMA-IR) level compared to placebo with weighted mean difference (WMD) of -0.545 (95% CI: -0.910, -0.18) mmol/L, I2 = 83.6% and -0.714(-1.388, -0.04), I2 = 84.4% respectively. There was no significant change in weighted mean difference of glycosylated hemoglobin A1C (HbA1c) % and lipid profiles (mmol/L). Meta-regression did not show any factor significantly affecting the treatment response. CONCLUSION: Cinnamon reduced FBG and HOMA-IR, level in T2DM and pre-diabetes patients compared to placebo. High heterogeneity observed among included studies warrants further clinical trials after standardization of cinnamon formulation.

Momordica charantia L. lowers elevated glycaemia in type 2 diabetes mellitus patients: Systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Momordica charantia Linnaeus (Cucurbitaceae) has been extensively used traditionally as food and herbal medicine for type 2 diabetes mellitus in Asia, Brazil, and east Africa. In vitro and in vivo studies suggest its glycemic control potential; however, clinical studies produced conflicting results. AIM OF THE STUDY: To evaluate the efficacy of M. charantia preparations in lowering elevated plasma glucose level in prediabetes and type 2 diabetes mellitus patients. METHODS: Electronic search of the Cochrane library, PubMed®, CINAHL, and SCOPUS databases was done from 1st January 1960-30th April 2018 without language restriction. Two independent reviewers extracted data and assessed risk of bias of articles. Revman var. 5.3 software was used for data synthesis in meta-analysis. Heterogeneity was assessed using Chi-square and I2 tests. Treatment effect was estimated using mean difference at follow up in outcome measures between M. charantia preparations and placebo or oral hypoglycemic agents control group. The protocol of this study has a registration number PROSPERO CRD42018083653. RESULTS: Ten studies of type 2 diabetes mellitus (n = 1045) were included in the meta-analysis. They had 4-16 weeks follow up and overall moderate to high risk of bias. Compared to placebo, M. charantia monoherbal formulation significantly reduces FPG, PPG and HBA1c with mean difference of - 0.72 mmol/L, (95% CI: -1.33, -0.12), I2 = 14%, - 1.43 mmol/L, (95% CI: -2.18, -0.67), I2 = 0, - 0.26%, (95% CI: -0.49, -0.03), I2 = 0 respectively. M. charantia also lowered FPG in prediabetes (mean difference -0.31 mmol/L, n = 52); the evidence was downgraded to low quality because the study had unclear risk of bias and inadequate sample size. No serious adverse effects were reported. CONCLUSION: M. charantia adjunct preparations improved glycemic control in T2DM patients. However, this conclusion is based on low to very low quality evidences for the primary outcomes and sparse data for several safety outcomes, thus, warrant further research. Particularly needed are the researches that focus on standardizing M. charantia formulation and determine its efficacy and safety in clinical trials with adequate sample size, designed with random sequence generation, allocation concealment of intervention and blinding of both research personnel and participants.

Safety and efficacy of Momordica charantia Linnaeus in pre-diabetes and type 2 diabetes mellitus patients: a systematic review and meta-analysis protocol.

BACKGROUND: Momordica charantia Linnaeus (Cucurbitaceae) has been used traditionally as a nutritious food and as a herbal medicine for type 2 diabetes mellitus. However, human studies that investigated its glycemic control have generated inconsistent findings. Therefore, this systematic review and meta-analysis is aimed at evaluating the safety and efficacy of M. charantia L. preparations in human studies that have investigated its role in glycemic control. METHODS: This protocol has been prepared according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The review will include randomized clinical trials and non-randomized clinical trials. The included studies will have assessed glycemic control of M. charantia preparations with placebo or standard oral anti-hyperglycemic agents in adult pre-diabetes and/or type 2 diabetes mellitus patients and have at least 4 weeks of follow-up. The primary outcomes of review are fasting blood glucose levels, glycosylated hemoglobin A1c, and post-prandial blood glucose level. Electronic database search for published literatures will be conducted without language restriction in EMBASE, MEDLINE/PubMed, the Cochrane Library, SCOPUS, Web of Sciences, and CINAHL databases. Search for gray literatures and references of the retrieved full-text articles will be conducted in Google, Google Scholar, OpenGrey, ProQuest dissertations & Theses, British Library EThos, and university digital library systems. Two independent reviewers will later evaluate full texts, extract data, and assess risk of bias of eligible articles. Publication biases will be assessed by testing asymmetry of funnel plot using Egger's or Begg's tests while heterogeneity will be assessed using Cochran Q test, P value, and I2. Revman software version 5.3 will be used for meta-analysis including subgroup and sensitivity analysis. DISCUSSION: This systematic review and meta-analysis will investigate both safety and efficacy of M. charantia preparations in type 2 diabetes mellitus. The review results will be published in a peer-reviewed journal. The results will bring better understanding of clinical outcomes in treatment of type 2 diabetes mellitus patients and highlight gaps for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018083653 .

Application of metabolomics to drug discovery and understanding the mechanisms of action of medicinal plants with anti-tuberculosis activity.

Human tuberculosis (TB) is amongst the oldest and deadliest human bacterial diseases that pose major health, social and economic burden at a global level. Current regimens for TB treatment are lengthy, expensive and ineffective to emerging drug resistant strains. Thus, there is an urgent need for identification and development of novel TB drugs and drug regimens with comprehensive and specific mechanisms of action. Many medicinal plants are traditionally used for TB treatment. While some of their phytochemical composition has been elucidated, their mechanisms of action are not well understood. Insufficient knowledge on Mycobacterium tuberculosis (M.tb) biology and the complex nature of its infection limit the effectiveness of current screening-based methods used for TB drug discovery. Nonetheless, application of metabolomics tools within the 'omics' approaches, could provide an alternative method of elucidating the mechanism of action of medicinal plants. Metabolomics aims at high throughput detection, quantification and identification of metabolites in biological samples. Changes in the concentration of specific metabolites in a biological sample indicate changes in the metabolic pathways. In this paper review and discuss novel methods that involve application of metabolomics to drug discovery and the understanding of mechanisms of action of medicinal plants with anti-TB activity. Current knowledge on TB infection, anti-TB drugs and mechanisms of action are also included. We further highlight metabolism of M. tuberculosis and the potential drug targets, as well as current approaches in the development of anti-TB drugs.