D-optimal mixture design optimized solid formulation containing fruits extracts of Momordica charantia and Abelmoschus esculentus.

Fruit extracts of Momordica charantia L. (Cucurbitaceae) and Abelmoschus esculentus (L.) Moench (Malvaceae) have shown promising antidiabetic activities in clinical trials. However, they remain underutilized due to insufficient standardization and lack of formulation containing their mixture. This study's overall purpose was to develop and optimize a capsule dosage form containing dried fruit extracts of M. charantia and A. esculentus. The design of the experiment involved two steps; first, response surface methodology (RSM) with a five-level two-factor central composite rotatable design (CCRD) was employed to determine the optimal dose of a mixture of extracts for adequate glycemic control. The extract of M. charantia and A. esculentus were the independent variables while fasting plasma glucose (FPG) was the dependent factor. In the second step, a D-optimal mixture design was applied to study the interaction effect of the optimal dose and selected excipients on granules flowability and capsules' disintegration time. Moreover, a second-order quadratic model determined the interrelationship of excipients and the desired capsules' quality attributes. The validity of the predicted models was confirmed. The findings indicated that a combined dose of 175 A. esculentus and 281 M. charantia (mg/kg) significantly reduced the FPG level compared to vehicle at day 14 (mean difference -2.7 ± 0.21, p < 0.001). This dose was used to make a 600 mg capsule (DM083) with 76% drug loading. The DM083 had 40.4 ± 0.62 mg GAE/gDW total polyphenols, 12 peaks HPLC fingerprint, and 26.6 ± 4.75 min average disintegration time. Together, these findings showed that a mixture of M. charantia and A. esculentus fruit extracts could be formulated in a stable capsule dosage form with acceptable quality standards. Further biological studies such as toxicity assays and long-term efficacy studies of the developed capsules could be carried out before large-scale commercial production.

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.

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.

Total polyphenols and antihyperglycemic activity of aqueous fruits extract of Abelmoschus esculentus: Modeling and optimization of extraction conditions.

Aqueous fruits extract of Abelmoschus esculentus (L.) Moench (Malvaceae) has been used traditionally in several communities to alleviate elevated blood glucose levels. However, optimized extraction conditions have not been reported. Thus, this study determined the optimal extraction conditions for extracting polyphenols from A. esculentus fruits and evaluated antihyperglycemic activity in vivo. Extraction time, temperature, and solid-to-solvent ratio were optimized using Response Surface Methodology (RSM). Total polyphenols and flavonoids were quantified using the Folin-Ciocalteu and aluminium chloride colorimetric methods, respectively. The fingerprint and quantification of quercetin-a major flavonoid with an antihyperglycemic effect was done using the chromatographic method. The antihyperglycemic activity was determined in a high-fat diet-Streptozotocin rat model. The rats were assigned to five groups (n = 6): Group 1 and 2 were normal and diabetic control received distilled water 1 mL/100g; Treatment group 3 and 4 received standardized A. esculentus fruit extract (AEFE) at a dose of 100 and 200 mg/kg, respectively; Group 5 received 5 mg/kg glibenclamide. All treatments were given orally for 14 days. Measurements of fasting plasma glucose (FPG) and body weight were done weekly. The RSM quadratic model predicted total polyphenols of 22.16 mg GAE/g DW. At optimal conditions of a solid-to-solvent ratio of 5%, extraction time 1 h, and extraction temperature of 70°C, confirmation experiments yield 20.2 [95% CI; 16.7 to 27.6] mg GAE/g DW, implying the model successfully predicted total polyphenols. The extract HPLC fingerprint showed 13 characteristic peaks with 0.45 ± 0.02 µg/g DW of quercetin. Compared with diabetic control, the standardized AEFE reduced FPG level dose-dependently (P < 0.001) with an EC50 of 141.4 mg/kg. Together, at optimal extraction conditions, extract with a high content of total polyphenols and good antihyperglycemic activity can be obtained. Studies are needed to identify additional polyphenolic compounds and determine their antidiabetic effects.

The anti-nociceptive effects of ethanol extract of aerial parts of Schkuhria pinnata in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The growing challenge to access conventional analgesics, contraindications, and adverse effects could have led individuals to use Schkuhria pinnata (Lam.) Kuntze ex Thell. (Compositae), as an alternative traditional therapeutic strategy for pain. However, evidence of its safety and efficacy is scarce. AIM OF THE STUDY: This study evaluated the anti-nociceptive effect of the ethanol extract of the aerial parts of S. pinnata in mice. METHODS: The mice were randomly assigned to nine groups: (1) vehicle; (2) acetylsalicylic acid (intraperitoneally 150 mg/kg); (3) pentazocine (intramuscularly 1.0 mg/kg); (4 a & b) orally 100 mg/kg extract; (5 a & b) orally 200 mg/kg extract; (6 a & b) orally 400 mg/kg extract. We used an acetic acid-induced writhing model and a tail-flick test. The number of writhes and time taken for the tail to flick was recorded. A one-way analysis of variance followed by Tamhane T2 post hoc was used for multiple comparisons. RESULTS: Compared to a vehicle (59.0 ± 2.68), S. pinnata ethanol extract at a dose of 200 and 400 mg/kg, p.o reduced writhes to 42.5 ± 1.12 and 27.0 ± 2.62, (p < 0.05) respectively. Similarly, the pain threshold of mice increased dose-dependently; doses of 200 and 400 mg/kg, increased time to 5.33 ± 0.42 and 8.67 ± 0.21 min, (p < 0.05) respectively. The extract had an EC50 of 348.8 mg/kg and acute toxicity established an LD50 of 1224.8 (95% CI: 952.2-1575.3). CONCLUSION: S. pinnata ethanol extract had anti-nociceptive activity by central and peripheral mechanisms that could justify its traditional use in pain management. Further studies could now focus on identifying active fractions and pure isolated compounds responsible for anti-nociceptive activity.

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.

Pharmacological reflection of plants traditionally used to manage diabetes mellitus in Tanzania.

ETHNOPHARMACOLOGICAL RELEVANCE: The increasing national prevalence of diabetes mellitus (DM) and its complications have overstretched the health care system in Tanzania and influenced patients to use herbal medicines as alternative therapeutic strategies. Therefore, an urgent need exists to validate the safety and efficacy of plants used locally. AIM OF THE STUDY: To identify plants used for the management of DM in Tanzania and analyses their pharmacological, phytochemistry, and safety evidence with a special focus on the mechanism of action. METHODS: Researchers searched Medline, web of science, and Scopus for published articles. Also, specialized herbarium documents of Muhimbili Institute of traditional medicine were reviewed. Articles were assessed for relevance, quality, and taxonomical accuracy before being critically reviewed. RESULTS: We identified 62 plant species used locally for DM management. Moringa oleifera Lam. and Cymbopogon citratus (D.C) stapf were the most mentioned. Fifty-four phytochemicals from 13 species had DM activities. These were mainly; polyphenolics, phytosterols, and triterpenoids. Extracts, fractions, and pure compounds from 18 species had in vitro antidiabetic activities of which 14 had α-glucosidase and α-amylase inhibition effects. The most studied -Momordica charantia L. increased; glucose uptake and adiponectin release in 3T3-L1 adipocytes, insulin secretion, insulin receptor substrate-1 (IRS-1), GLUT-4 translocation, and GLP-1 secretion; and inhibited protein tyrosine phosphatase 1 B (PTP1B). Preclinical studies reported 30 species that lower plasma glucose with molecular targets in the liver, skeletal muscles, adipose tissues, pancreases, and stomach. While three species; Aspilia mossambiscensis (Oliv.) Willd, Caesalpinia bonduc (L.) Roxb, and Phyllanthus amarus Schumach. & Thonn. had mild toxicity in animals, 33 had no report of their efficacy in DM management or toxicity. CONCLUSION: Local communities in Tanzania use herbal medicine for the management of DM. However, only a fraction of such species has scientific evidence. A. mossambiscensis, C. bonduc., and P. amarus had mild toxicity in animals. Together, our findings call for future researches to focus on in vitro, in vivo, and phytochemical investigation of plant species for which their use in DM among the local communities in Tanzania have not been validated.

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.

Systematic review and meta-analysis protocol for efficacy and safety of Momordica charantia L. on animal models of type 2 diabetes mellitus.

BACKGROUND: Studies on several preclinical models of type 2 diabetes mellitus have been conducted to establish the hypoglycemic activity of Momordica charantia L. Concerned with appropriateness of these models, we designed a systematic review to establish the efficacy and safety of M. charantia L. in preclinical models of type 2 diabetes mellitus. METHODS: Review authors will search without language restriction in MEDLINE/PubMed, Web of Science, Embase, Scopus, and CINAHL databases through April 2019. Search filters will be applied to enhance search efficiency. The authors will search for gray literature in Google and Google Scholar, OpenGrey, and ProQuest Dissertations & Theses. Two authors will evaluate full texts, extract data, and asses risk of bias independently. The review will include randomized or non-randomized studies that assessed the efficacy or safety of M. charantia L. with vehicle control group. The primary endpoint will be fasting blood glucose level. We will use Egger's test to assess publication biases. Chi-square test and I2 will be used to assess heterogeneity in effect size of the primary outcome. Using RevMan software version 5.3, the authors will perform a meta-analysis of quantitative data. DISCUSSION: The strength of evidence will be rated as high, moderate, low, or very low using GRADE framework for animal studies. This systematic review will potentially improve research practice by identifying risks of bias and design features that compromise translatability and contribute to evidence-based clinical trial design. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019119181.

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 .

Efficacy of standardized extract of Hibiscus sabdariffa L. (Malvaceae) in improving iron status of adults in malaria endemic area: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous community of Mkuranga district have been using aqueous extract of H. sabdariffa L. for treating anemia. However, there have been neither safety nor efficacy studies to validate this medicinal product in anemia. AIM: The purpose of this study was to establish efficacy and safety of standardized aqueous extract of H. sabdariffa L. in anemic adults. MATERIALS AND METHODS: This was a randomized controlled clinical trial in which 130 adults' men and women aged 18-50 years were involved after meeting the inclusion criteria. Initially, standardized aqueous extract of H. sabdariffa L. was prepared using optimized extraction parameters. Stratified randomization was used to randomize participants into four fixed dose groups. The first group received oral dose of 1000ml while the 2nd group was randomized to receive 1500ml orally. The last two groups were given a dose of 2000ml of extract and 200mg ferrous sulphate tablet respectively. Primary endpoint was the actual change of iron status indicators at the end of 30 days follow up period as compared to those recorded at baseline. Adverse effects were assessed at every 10th day scheduled visit. In all arms, HB and hematopoietic parameters were measured using HemoCue hemoglobinometer® (HemoCue, Ängelholm, Sweden) and hematology analyzer® respectively at the trial site. Follow up was done for 30 days. A total of 82 participants were included for analysis. RESULTS: A standardized aqueous extract of H. sabdariffa L. did not improve iron status in anemic adults in malaria endemic region (P>0.005). However, there was evidence to support the safety of the extract for human consumptions as herbal supplement. Iron and organic acids contents of H. sabdariffa L. extract showed the potential of improving hematopoietic parameters. Studies with bigger sample size are therefore needed to establish the efficacy of the extract when concurrently used with malaria chemoprophylaxis in malaria endemic areas.

Ethno-medicinal knowledge and plants traditionally used to treat anemia in Tanzania: a cross sectional survey.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous communities have often served as rich repositories of empirical knowledge on medicinal plants used for anemia. Use of these plants need to be validated with respect to their efficacy and safety so as to provide scientific basis of their use. Quantifying presence of medicinal plants used for anemia treatment, validating indigenous knowledge and extent of its use in rural Mkuranga district, Tanzania is the main focus of this paper. METHODS: A cross sectional study conducted in May and December 2013 at Mkuranga District of Coastal region of Tanzania. Forty key informants including traditional healers, religious leaders, community members and healthcare workers were interviewed using semi structured questionnaire. Eight focus group discussions were also conducted. Both interviews and focus group discussion gathered data on socio-demographics, general knowledge of anemia and plants used to correct anemia. In a brief field visit, all plants mentioned during the interview were collected and later identified. Both NVivo 10 and STATA softwares were employed for statistical analysis. RESULTS: Out of 40 participants, 31 were traditional healers, majority were male (77.4%). Mean age of the participants was 55.7±15 years. About 45% had no any formal education and majority (80%) were married. Twenty eight plant species are used to treat anemia. Hibiscus sabdariffa was the most mentioned species. The species belongs to 24 families, with Euphorbiaceae (14.3%) having the largest number. Lawsonia inermis, Aloe sp, Uvaria acuminata, Parinari curatellifolia, Ozoroa reticulata, Manihot esculenta, Canthium sp and Afzelia quanzensis were the plant species in which their claimed use for anemia were novel. CONCLUSIONS: People in rural areas of Mkuranga district possess a rich traditional knowledge of medicinal plants species for anemia treatment. Researches on these plants showed promising anti-anemic activity. Analysis and documentation of this knowledge has not only helped the analysis and recognition of novel information, it also contributed to conserving it for future generations.