Safety profile of herbal medicines submitted for marketing authorization in Tanzania: a cross-sectional retrospective study.

BACKGROUND: The popular use of herbal medicines necessitates national regulatory authorities to have efficient mechanisms for the control of these products including marketing authorization (MA) and safety follow-up. Herbal medicines like conventional medicines require assessment of efficacy, safety and quality information before MA can be granted. However, the complete proof of safety is mainly based on the history of the long-term traditional use. Herbal medicines can cause adverse reactions due to various factors and thus require clinical trials to ensure their safety. Herbal medicines treatment practices involve combinations of different plants to achieve the desired effect while multiple herbal components have been known to cause herbal-herbal toxicity and interactions due to variety of complex active ingredients in plants. Compliance with regulatory requirements on herbal medicines has been shown to be difficult for manufacturers since different countries have different regulatory requirements with wide variations which results in the MA of very few herbal medicines. Limited studies on dossiers of marketing authorization of herbal medicines have been performed in other countries, with no studies in African regulatory system settings. The aim of this study is to determine the type of safety documentation that is submitted on herbal medicines application dossiers to support MA in Tanzania. METHODS: A cross-sectional retrospective study of herbal medicines dossiers submitted at the Tanzania Medicines and Medical Devices Authority from 2009 to 2020 was conducted. RESULTS: As many as 75% of the herbal products applications were combination products made by more than one herbal substance or plant. Out of 84 dossiers subjected to analysis the majority did not provide evidence of preclinical (55%) and clinical safety data (68%). Evidence of safety data in humans was mostly from the literature (70%) and not manufacturers' clinical studies. Quality parameters with safety implications were not included in 48% and 23% of the active herbal substance and finished product specifications, respectively. CONCLUSION: Analysis of the herbal medicine dossiers submitted showed major deficiencies of safety data to support MA. Manufactures need to provide evidence to support the safety of their products for evidence-based regulatory decisions and to avoid multiple reviews of the applications.

Insects as Diet and Therapy: Perspectives on Their Use for Combating Diabetes Mellitus in Tanzania.

More than 450 million people worldwide are suffering from diabetes and this number is expected to increase. In developing countries, such as Tanzania, the number of patients suffering from diabetes and associated diseases is increasing as well. Up to 80% of the Tanzanian people rely on traditional medicines for their health care services. The nature of Tanzanian is very rich in different plant and insect species, and this could be exploited through their implementation in preventive and/or curative approaches in the battle against diabetes. The implementation of healthy insects in the diets of people may help in the prevention of obesity, which is a risk factor in the etiology of diabetes, while the identification of small molecules in insects may help in the discovery of potential new drugs that can be used in the treatment of diabetes. In this paper, an overview on the potential implementation of insects against diabetes is presented.

Ethnomedical survey and safety evaluation of traditional eye medicines used in Misungwi district, Tanzania.

AIM: This study aimed at documenting products used as traditional eye medicine (TEM) in Misungwi district, Tanzania, and performing preliminary analysis on safety status. METHODOLOGY: Ethnomedical study was conducted in Misungwi district. Information was sourced by face-to-face interview with traditional healers, traditional medicine vendors, and knowledgeable people guided by a well-structured questionnaire. Safety was evaluated by determining pH using pH meter and mineral analysis using the Delta, Portable X-ray fluorescence equipment, and qualitative chemical tests. RESULTS: A total of 23 TEM products were recorded from botanical (79%) and zoological (21%) sources including animal excreta. Liquid preparation ranked highest among dosage forms. Safety evaluation showed that only one product possessed the pH value of 7.4 as recommended for topical ophthalmic medicines. Fourteen minerals were detected and quantified in three samples; some of these minerals are known for their negative effects to the eyes, of medical interest is strontium used for the management of benign eye tumors. Information providers were unaware of health risks associated with the use of TEM. CONCLUSION: This study has revealed the common use of TEM in Misungwi district. The majority of the products are from the botanical source. Although literature provides supporting data for the application to some of the recorded TEM, safety evaluation by pH and mineral analysis in this study have indicated possible ophthalmological medical problems that could result from using such products. Extensive scientific studies including animal experiments and identification of bioactive compounds are essential to develop safe TEMs.

Rapid isolation and identification of minor natural products by LC-MS, LC-SPE-NMR and ECD: isoflavanones, biflavanones and bisdihydrocoumarins from Ormocarpum kirkii.

The combination of the hyphenated techniques LC-MS and LC-SPE-NMR constitutes a powerful platform for the rapid isolation and identification of minor components from natural sources. Electronic circular dichroism (ECD) is a useful tool to determine the absolute configuration of small quantities of chiral molecules. In order to search for minor constituents present in an Ormocarpum kirkii extract, these techniques were applied for the separation and structure elucidation of a series of isoflavanones, biflavanones and biscoumarins. After optimization of chromatographic conditions and subsequent isolation, MS and 1D and 2D NMR data were collected. Experimental and calculated ECD spectra were used in conjunction with NMR data to confirm the absolute configuration of these compounds. Eight compounds were identified for the first time and six have been previously reported. The present approach offers a strategy for accelerating research on natural products.

Herbal medicines and infectious diseases: characterization by LC-SPE-NMR of some medicinal plant extracts used against malaria.

The extracts of two medicinal plants used in traditionalmedicine against malariawere characterized by means of an LC­SPE­NMR and LC­MS platform. The structure of a series of major constituents from Bafodeya benna, as well as minor constituents from Ormocarpum kirkii, was determined. Bafodeya benna was found to contain (2R,3R)-taxifolin-3-O-α-L-rhamnoside or astilbin, and its isomers neoastilbin, neoisoastilbin, and isoastilbin, as well as quercetin-3-O-α-L-rhamnoside. From Ormocarpum kirkii, a series of known flavonoids and biflavonoids was obtained, as well as three new compounds, i.e., 7,7''-di-O-ß-D-glucosyl-(−)-chamaejasmin, 7-O-ß-D-glucosyl-(I-3,II-3)-biliquiritigenin, and isovitexin-(I-3,II-3)-naringenin. The isolated constituents may explain, at least in part, the traditional use against malaria. LC­SPE­NMR, in combination with LC­MS, is a powerful tool for the fast characterization of plant extracts, in order to define priorities at an early stage of a fractionation procedure. In addition, herbal medicinal products can completely be characterized, both with regard to their major as well as their minor constituents.

Phytochemical and biological investigations of Elaeodendron schlechteranum.

AIM OF THE STUDY: Elaeodendron schlechteranum (Loes.) Loes. is a shrub or tree belonging to the family Celastraceae. In Tanzania, in addition to ethnopharmacological claims in treating various non-infectious diseases, the root and stem bark powder is applied on septic wounds, and the leaf paste is used for treatment of boils and carbuncles. The aim of this study was to identify the putative active constituents of the plant. MATERIALS AND METHODS: Dried and powdered root bark was extracted and subjected to bioassay-guided fractionation, based on antibacterial, antiparasitic and anti-HIV activity. Isolated compounds were identified by spectroscopic methods, and evaluated for biological activity. RESULTS AND CONCLUSIONS: Bioassay-guided isolation led to the identification of tingenin B (22beta-hydroxytingenone) as the main antibacterial constituent. It was active against Bacillus cereus, Staphylococcus aureus and Escherichia coli (IC(50)<0.25 microg/mL). Furthermore, antiparasitic activity was observed against Trypanosoma cruzi (IC(50)<0.25 microg/mL), Trypanosoma brucei (<0.25 microg/mL), Leishmania infantum (0.51 microg/mL), and Plasmodium falciparum (0.36 microg/mL). Tingenin B was highly cytotoxic to MRC-5 cells (CC(50) 0.45 microg/mL), indicating a poor selectivity. Two inactive triterpenes, 3beta,29-dihydroxyglutin-5-ene and cangoronine methyl ester were also obtained. Phytochemical investigation of the anti-HIV active fractions led to the isolation and identification of three phenolic compounds, namely 4'-O-methylepigallocatechin, 4'-O-methylgallocatechin, and a new procyanidin dimer, i.e. 4',4'''-di-O-methyl-prodelphinidin B(4) or 4'-O-methylgallocatechin-(4alpha-->8)-4'-O-methylepigallocatechin. However, none of these showed anti-HIV activity.

Antiplasmodial activity of (I-3,II-3)-biflavonoids and other constituents from Ormocarpum kirkii.

Preliminary screening of a series of medicinal plants, traditionally used in Tanzania, showed an IC(50) of 15.6-31.2 microg/ml for the crude extract of the root of Ormocarpum kirkii S. Moore (Papilionaceae) against Plasmodium falciparum. A bioguided isolation was performed in order to isolate the active constituents. Twelve constituents were obtained and identified using NMR and MS data, and optical rotation measurements. The compounds comprised seven (I-3,II-3)-biflavonoids, three (I-3,II-3)-bi-4-phenyldihydrocoumarins, an isoflavanone and a C-glucosylated flavone. Six compounds, liquiritigeninyl-(I-3,II-3)-naringenin, apigeninyl-(I-3,II-3)-naringenin, 7-O-beta-D-glucopyranosylchamaejasmin, (3R,4S,3''R,4''S)-5,5''-di-O-methyldiphysin, 7-O-beta-D-glucopyranosyldiphysin, and 4''-hydroxydiphysolone, were isolated in addition to six known components. The compounds were evaluated for antimicrobial activity in a broad screening panel, including P. falciparum. Seven of these showed antiplasmodial activity; isochamaejasmin being the most active with an IC(50) of 7.3+/-3.8 microM, but the selectivity was rather limited. Thus, these constituents may contribute, at least in part, to the antimalarial use of O. kirkii in traditional medicine.

Screening of Tanzanian medicinal plants against Plasmodium falciparum and human immunodeficiency virus.

Medicinal plants used to treat infectious diseases in Bunda district, Tanzania, were screened for activity against Plasmodium falciparum and Human Immunodeficiency Virus Type 1 (HIV-1, IIIB strain) and Type 2 (HIV-2, ROD strain). Antiplasmodial activity was observed for the 80 % MeOH extract of Ormocarpum kirkii (root; MIC = 31.25 microg/mL), Combretum adenogonium (leaves), Euphorbia tirucalli (root), Harrisonia abyssinica (root), Rhynchosia sublobata (root), Sesbania sesban (root), Tithonia diversifolia (leaves), and Vernonia cinerascens (leaves; MIC value of 62.5 microg/mL). With regard to HIV, 80 % MeOH extracts of Barleria eranthemoides (root), Combretum adenogonium (leaves and stem bark), Elaeodedron schlechteranum (stem bark and root bark), Lannea schweinfurthii (stem bark), Terminalia mollis (stem bark and root bark), Acacia tortilis (stem bark), Ficus cycamorus (stem bark) and Indigofera colutea (shoot), as well as H2O extracts from Barleria eranthemoides (root), Combretum adenogonium (leaves and stem bark), and Terminalia mollis (stem bark and root bark) exhibited IC50 values below 10 microg/mL against HIV-1 (IIIB strain). The highest anti-HIV-1 activity value was obtained for the B. eranthemoides 80 % MeOH root extract (IC50 value 2.1 microg/mL). Only a few extracts were active against HIV-2, such as the 80 % MeOH extract from Lannea schweinfurthii (stem bark) and Elaeodedron schlechteranum (root bark), showing IC50 values < 10 microg/mL.

Screening of some Tanzanian medicinal plants from Bunda district for antibacterial, antifungal and antiviral activities.

Extracts from 50 plant parts obtained from 39 different plants belonging to 22 families used to treat infectious diseases in Bunda district, Tanzania, were screened against twelve microorganisms, including the bacteria Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella typhimurium, the fungi Aspergillus niger, Candida albicans, and the viruses Herpes Simplex Virus type 1, Vesicular Stomatitis Virus T2, Coxsackie B2 and Semliki Forest A7. The highest activity was obtained for the n-hexane extract of Elaeodendron schlechteranum root bark against the Gram-positive bacteria Bacillus cereus (MIC 0.97 microg/ml and MBC 1.95 microg/ml) and Staphylococcus aureus (MIC 3.90 microg/ml and MBC 31.25 microg/ml). Gram-negative bacteria were less sensitive. Only Balanites aegyptiaca stem bark exhibited a high antifungal activity against Candida albicans (MIC 125 microg/ml and MFC 250 microg/ml). Extracts from four plants; Lannea schweinfurthii, Combretum adenogonium, Ficus sycomorus and Terminalia mollis showed strong antiviral activity with RF values of 10(3) and 10(4) against Herpes Simplex Virus type 1 at various concentrations. Our results support, at least in part, the use of most plants as claimed by traditional healers/informants especially against the Gram-positive bacteria Bacillus cereus and Staphylococcus aureus.

Ethnopharmacological survey of the Bunda district, Tanzania: plants used to treat infectious diseases.

An ethnobotanical study was carried out in six villages in the Bunda district, Mara Region, Tanzania, where the use of plants still has a special meaning to the society, in the treatment of various diseases. Information was obtained from the traditional healers and other experienced persons, having some knowledge on medicinal plants. Fifty-two plants were reported for use in the treatment of various infectious diseases. These plants belong to 29 families, with Papilionaceae being the most represented. Leaves ranked the highest, especially for use in topical preparations. Oral administration was the most frequently used route of administration. Twenty-one percent of the recorded plants were reported for treating venereal diseases, with syphilis and gonorrhea being the most commonly mentioned. Information providers requested feedback with regard to the plants proven scientifically to be toxic in order to avoid risks while offering their services. From this work it was found out that, people in this area commonly use medicinal plants with trust they have built on the curative outcome witnessed. As the first ethnobotanical study in Bunda district recording 52 plants in a small area covered, publication of this work is expected to open up more studies to record many useful medicinal plants unfolded.