Dataset on the geographical distribution of species of the genus Solanum, subgenus Leptostemonum in Uganda.

The dataset includes the diversity, occurrence points and a distribution map of species of the subgenus Leptostemonum in Uganda. The data was obtained following field surveys carried out in various parts of Uganda. These were guided by distribution data retrieved from Makerere University Herbarium and Flora of Tropical East Africa (FTEA). At each sampling site, species name, altitude and habitat type were recorded. Occurrence points were geocoded using a hand-held GPS (a ≤ 5M Germin S90 GPS). The distribution map was generated using ArcMap 10.7.1 software. The dataset consists of 172 occurrence points representing 18 species of subgenus Leptostemonum that occur in Uganda. The data can be used to assess the effect of climate change on the diversity and distribution of these species. The data set is also important for informing resource users, conservationists and policy makers about the biodiversity hotspots of these economically important species.

Acute and subacute toxicity profile of ethanolic stem bark extract of Albizia coriaria Welw. ex Oliv. in Wistar albino rats.

Albizia coriaria (Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of A. coriaria in mature healthy Wistar albino rats following Lorke's method and OECD guidelines 407. The LD50 of the ethanolic stem bark extract of A. coriaria was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of A. coriaria was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg.

Network analysis and molecular docking studies of quercetin as a potential treatment for prostate cancer.

Globally, the prevalence of prostate cancer is only the second to lung cancer. In Africa however, the commonest cancer among men is cancer of the prostate. The use of natural compounds from plants such as quercetin is being explored as a potential cure. Quercetin is a plant-based flavonoid that has anti-inflammatory, antioxidant and anticancer properties. Although quercetin has been extensively studied, its chemo preventive mode of action is not well-understood. The molecular targets and potential mechanisms underlying the action of quercetin against prostate cancer were identified and validated using network pharmacology and molecular docking methods. The biological targets of quercetin and targets associated with prostate cancer were obtained through database mining. Overlapping targets associated with quercetin and prostate cancer were identified and used to construct a compound-disease target (C-D) network and the targets were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction analysis (PPI). A disease target- pathway network was constructed and then merged with C-D network to form a compound-disease_target-pathway (C-D-P) network. Hub targets were obtained from the C-D-P and PPI networks. The binding affinities between quercetin and the retrieved hub targets were identified. Pathway enrichment analysis showed that prostate cancer associated quercetin targets were mainly linked with pathways such as the cancer signaling pathways (HIF-1 and ErbB) and hepatitis B. Basing on the PPI and C-D-P network analysis STAT3, TP53, MAPK1, MAPK3 and KRAS were identified as the main targets and were subjected to molecular docking. The results showed quercetin's ability to stably bind to the key targets. In conclusion, this study showed the potential molecular targets and mode of action of quercetin in prostate cancer treatment. This can potentially inform the future use of quercetin in the treatment of prostate cancer.

Application of the herbal chemical marker ranking system (Herb MaRS) to the standardization of herbal raw materials: a case study.

INTRODUCTION: Phytochemical standardization of herbal materials involves establishing consistent levels of one or more active ingredients or markers. It ensures the authenticity and quality of herbal materials, extracts, and their products. This research aimed to apply the herbal chemical marker ranking system (Herb MaRS) originally proposed for quality assurance of complex herbal products to establish markers for controlling the quality of herbal raw materials. METHODS: The assessment of compounds for suitability as markers was based on the Herb MaRS, with minor modifications as follows: for more objective scoring, evidence of biological activity of the potential marker compound(s) was determined at three levels based on the number of symptoms of the disease condition a compound can treat or alleviate: (i) one symptom (1 point), two symptoms (2 points), and 3 or more symptoms (3 points). The reported concentrations of the compounds were also scored as follows: concentration not determined (0 points), concentration ≥ 5 ppm (1 point), concentration ≥ 50 ppm (2 points) and availability of analytical standards (1 point). Finally, the compounds were scored for the availability of an analytical method (1 point). The compounds were scored from 0 to 8, where 8 indicated the most suitable chemical marker. RESULTS: The selected markers were as follows: aromadendrine, α-terpineol, globulol, and 1,8-cineol (in Eucalyptus globulus Labill. ); aloin, aloe emodin, acemannan (in Aloe barbadensis (L.) Burm.f. ), lupeol, lupenone, betulinic acid, betulin, and catechin (in Albizia coriaria Oliv.); mangiferin, catechin, quercetin, and gallic acid (in Mangifera indica L.); polygodial (in Warburgia ugandensis Sprague); azadirachtin, nimbin, nimbidin (in Azadirachta indica A. Juss. ); and 6,8,10-gingerols, and 6-shogaol (in Zingiber officinalis Roscoe). CONCLUSIONS: Herb MaRS can be efficiently applied to select marker compounds for quality control of herbal materials. However, for herbs whose phytochemicals have not been sufficiently researched, it is difficult to establish evidence of activity, and there are no analytical standards and/or methods; this is the case for plants exclusively used in Africa. The markers identified should be incorporated into chromatographic fingerprints, their quantitative methods developed, and evaluated for applicability at the various stages of the production chain of herbal medicines; then, they can be included in future local plant monographs. There is also a need to build local capacity to isolate marker compounds, particularly those that are not sold by current vendors.

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.

Inorganic nutrients and heavy metals in some wild edible plants consumed by rural communities in Northern Uganda: Implications for human health.

For centuries, wild edible plant species have sustained local communities across Africa by supplementing households' diets in seasons of food shortage. Wild edible plants contain inorganic nutrients, which are essential for the proper functioning of organisms. However, their nutritional contents have not been well researched and are generally poorly understood. This study aimed to quantify the levels of inorganic micro-and macronutrients as well as heavy metals (Mg, Ca, K, Fe, Zn, Cd, Hg and Pb) in selected wild edible plants traditionally consumed among the Acholi communities in northern Uganda, and associated health risks of consuming them. The leaves and young stems of 12 wild edible plants, viz: Acalypha rhomboidea, Asystacia gangetica, Crassocephalum sacrobasis, Crotalaria ochroleuca, Heterotis rotundifolia, Hibiscus cannabinus, Hibiscus sp., Hibiscus surattensis, Ipomoea eriocarpa, Maerua angolensis, Senna obtusifolia and Vigna membranacea were air-dried and crushed to powder. The powders were then macerated using aqua regia solution and analyzed in triplicates using the Atomic Absorption Spectrophotometry (AAS). The target hazard quotient (THQ) of Pb was calculated for non-carcinogenic health risks. Mg, Ca, K, Fe, Zn and Pb were detectable in all the wild edible plants sampled. All inorganic nutrients (mg/100gdw), were below the Recommended Daily Allowance (RDA); Mg (9.4 ± 0.19 to 10.4 ± 0.15), Ca (119 ± 5.82 to 1265 ± 14.9), Fe (3.29 ± 0.02 to 11.2 ± 0.09), Zn (0.52 ± 0.02 to 2.36 ± 0.03). Hg and Cd were below detectable limits in all the samples tested. The content of Pb (0.69 ± 0.11 to1.22 ± 0.07) was higher than the CODEX and EU limits of 0.1 ppm (0.001 mg/g) but was below the recommended threshold of 1. The health risk assessment revealed no potential hazards both in children and adults. However, there is a need to study the bioavailability of Pb when the vegetables are consumed due to factors such as indigestion and antinutritional compounds.

Medicinal plants used for treatment of malaria by indigenous communities of Tororo District, Eastern Uganda.

BACKGROUND: Malaria remains the leading cause of death in sub-Saharan Africa. Although recent developments such as malaria vaccine trials inspire optimism, the search for novel antimalarial drugs is urgently needed to control the mounting resistance of Plasmodium species to the available therapies. The present study was conducted to document ethnobotanical knowledge on the plants used to treat symptoms of malaria in Tororo district, a malaria-endemic region of Eastern Uganda. METHODS: An ethnobotanical study was carried out between February 2020 and September 2020 in 12 randomly selected villages of Tororo district. In total, 151 respondents (21 herbalists and 130 non-herbalists) were selected using multistage random sampling method. Their awareness of malaria, treatment-seeking behaviour and herbal treatment practices were obtained using semi-structured questionnaires and focus group discussions. Data were analysed using descriptive statistics, paired comparison, preference ranking and informant consensus factor. RESULTS: A total of 45 plant species belonging to 26 families and 44 genera were used in the preparation of herbal medicines for management of malaria and its symptoms. The most frequently mentioned plant species were Vernonia amygdalina, Chamaecrista nigricans, Aloe nobilis, Warburgia ugandensis, Abrus precatorius, Kedrostis foetidissima, Senna occidentalis, Azadirachta indica and Mangifera indica. Leaves (67.3%) were the most used plant part while maceration (56%) was the major method of herbal remedy preparation. Oral route was the predominant mode of administration with inconsistencies in the posology prescribed. CONCLUSION: This study showed that the identified medicinal plants in Tororo district, Uganda, are potential sources of new antimalarial drugs. This provides a basis for investigating the antimalarial efficacy, phytochemistry and toxicity of the unstudied species with high percentage use values to validate their use in the management of malaria.

In Vitro Anti-Venom Potentials of Aqueous Extract and Oils of Toona ciliata M. Roem against Cobra Venom and Chemical Constituents of Oils.

There are high mortality and morbidity rates from poisonous snakebites globally. Many medicinal plants are locally used for snakebite treatment in Uganda. This study aimed to determine the in vitro anti-venom activities of aqueous extract and oils of Toona ciliata against Naja melanoleuca venom. A mixture of venom and extract was administered intramuscularly in rats. Anticoagulant, antiphospholipase A2 (PLA2) inhibition assay, and gel electrophoresis for anti-venom activities of oils were done. The chemical constituents of the oils of ciliata were identified using Gas chromatography-tandem mass spectroscopy (GC-MS/MS). The LD50 of the venom was 0.168 ± 0.21 µg/g. The venom and aqueous extract mixture (1.25 µg/g and 3.5 mg/g) did not cause any rat mortality, while the control with venom only (1.25 µg/g) caused death in 1 h. The aqueous extract of T. ciliata inhibited the anticoagulation activity of N. melanoleuca venom from 18.58 min. to 4.83 min and reduced the hemolytic halo diameter from 24 to 22 mm. SDS-PAGE gel electrophoresis showed that oils completely cleared venom proteins. GC-MS/MS analysis showed that the oils had sesquiterpene hydrocarbons (60%) in the volatile oil (VO) and oxygenated sesquiterpenes (48.89%) in the non-volatile oils (NVO). Some major compounds reported for the first time in T. ciliata NVOs were: Rutamarin (52.55%), ß-Himachalol (9.53%), Girinimbine (6.68%) and Oprea1 (6.24%). Most compounds in the VO were reported for the first time in T. ciliata, including the major ones Santalene (8.55%) and Himachal-7-ol (6.69%). The result showed that aqueous extract and oils of T. ciliata have anti-venom/procoagulant activities and completely neutralized the venom. We recommend a study on isolation and testing the pure compounds against the same venom.

Phytochemical composition and antioxidant activities of some wild edible plants locally consumed by rural communities in northern Uganda.

Background: Acalypha rhomboidea, Asystacia gangetica, Crassocephalum sacrobasis, Crotalaria ochroleuca, Heterosis rotundifolia, Hibiscus cannabinus, Hibiscus sp., Hibiscus surratensis, Ipomoea eriocarpa, Maerua angolensis, Senna obtusifolia and Vigna membranacea are among the common wild edible plants in the Acholi sub-region, northern Uganda. This study evaluated the phytochemical constituents and antioxidant potential of the plants. Methods: Fresh leaves collected from each plant species were air-dried under shade. The phytochemical contents of the ethanol and petroleum ether extracts were determined using standard protocols. The antioxidant content of the methanolic extracts was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Results: Preliminary phytochemical analyses indicated the presence of tannins, reducing compounds, alkaloids, flavonoids, flavons aglycones, flavanosides, anthracenosides, anthocyanosides, volatile oils, coumarins, steroid glycosides, sterols and triterpenes. However, the extracts did not contain any emodols and saponins. The results of the quantitative phytochemical analysis showed that the contents of different phytochemicals detected varied significantly (p < 0.05) among the selected plants. The amount of tannins in mg/g (gallic acid equivalent) of dry weight varied from 3.90 ± 0.16 in C. ochroleuca to 10.41 ± 0.78 in I. eriocarpa, total flavonoids in RE, mg/g dry matter from 4.07 ± 0.11 in I. eriocarpa to 14.94 ± 0.08 in S. obtusifolia. Total alkaloids in mg/100 g ranged from 1.59 ± 0.30 in I. eriocarpa to 6.37 ± 0.24 in Hibiscus sp. Total phenolic content in GAE, mg/g dry matter ranged from 13.39 ± 0.26 in A. rhomboidea to 64.25 ± 0.54 in I. eriocarpa. The in vitro antioxidant assays revealed substantial free radical scavenging activity in all the plants. Antioxidant activity expressed as IC50 (ppm) ranged from 13.39 for A. rhomboidea to 64.84 for I. eriocarpa, compared to 12.82 for ascorbic acid standard. The total phenolic compounds and total tannins had significant and positive correlations with DPPH free radical scavenging activity. Conclusion: The findings of this study provide evidence that the species are good natural sources of phytochemicals and antioxidants, whose regular consumption could provide human health benefits by protecting against oxidative stress related diseases. Further research is needed on the structural characterization of the phytochemicals, profiling the plant extracts with high antioxidant activity and determining the antimicrobial activities.

Bioactivity and toxicity of coumarins from African medicinal plants.

Introduction: Coumarins are naturally occuring metabolites from plants and a few micro-organisms. They have been widely used in the food and drug industry in their natural or synthetic forms. Numerous coumarins possess several biological activities such as anti-inflammatory, anti-ulcers, anti-tumour, anti-microbial, anti-coagulant. The aim of this study was to assess the bioactivity, and toxicity of coumarins from African medicinal plants. Methods: We searched online databases and search engines such as PubMed, Google Scholar and Web of Science for key terms such as coumarins, toxicity, bioavailability, bioactivity with appropriate Boolean operators. Only full-length research articles published in English between 1956 to 2023 were reviewed. Results: We recorded 22 coumarins from 15 plant species from Africa. Most of the plant species (33%) were from North Africa. These were followed by East Africa at 21%, then West, and Central Africa at 18.2% each. Most of the coumarins (21.3%) were isolated from the entire plant and the leaves (19.1%) and most of them (46.7%) had some antimicrobial activity. Five coumarins viz osthole, pseudocordatolide C & calanolide, chartreusin and esculetin had either antitumor or anticancer activity. Six coumarins had varying levels and types of toxicity ranging from inhibiting blood clotting as anticoagulants, to cytotoxic effects, causing hyperventilation, tremor, & photophobia, pulmonary haemorrhage, carcinogenic activity, severe neurotoxicity, hepato- and phototoxicity. Conclusion: Several African medicinal plants are sources of various coumarins that possess several biological activities as well as toxicities. This calls for more research into their safety and efficacy because of their wide spread applications as therapeutic agents.

Ethnobotanical study of medicinal plants utilized in the management of candidiasis in Northern Uganda.

BACKGROUND: The emergence of resistant Candida species to antifungal drugs has led to resurgence in herbal usage globally. However, little is known about anti-candida plants. This study explored ethnomedicinal plants as treatment option for candidiasis in Pader, Northern Uganda. METHODS: A cross-sectional survey of potential anti-candida plants was conducted using questionnaires, focus group discussions and field observations in March 2022. Sixty-three respondents were selected by snowball technique. The frequencies of respondents/responses were analyzed, associations of respondents' socio-demographics with indigenous knowledge of herbal usage established by Chi-square (χ2) test using SPSS 27. Informant Consensus Factor was computed to establish level of agreement on herbal usage, and thematic analysis done for focus group discussions. RESULTS: Candidiasis is still common and troublesome in Pader. All herbalist had equal chances of receiving and treating candidiasis patients irrespective of herbalist's gender, age, education level, occupation, marital status and religion (p > 0.05). About 39.7% of herbalists received candidiasis patients weekly (p < 0.01). All herbalists had knowledge on candidiasis. Death (56.8%) and discomfort (36.8%) were the major health risks of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC), respectively. A total of 32 potential anti-candida plant species in 18 families were identified. Families of Fabaceae (9 species) and Asteraceae (5 species) had most plant species. Trees (50.0%) and herbs (43.8%) were the dominant life forms. The commonest plants by frequency of mention were: Momordica foetida (26), Sansevieria dawei (20), Khaya anthotheca (15), Piliostigma thonningii (10), Clerodendrum umbellatum (7), Hallea rubrostipulata (5) and unidentified plant, 'Agaba/daa layata' in Acholi dialect (5). Plant parts mainly used were roots (56.3%) and stem barks (15.6%) harvested majorly by cutting (46.9%) and uprooting (12.5%). Most respondents (females, 95%) preferred herbal to western medication (p < 0.01) due to its perceived effectiveness. There was high consensus among herbalists on herbal remedies for OPC and VVC (FIC = 0.9). CONCLUSIONS:  Pader communities have diverse indigenous knowledge on candidiasis and prefer herbal medicines to orthodox treatment for candidiasis. However, the herbalists use unsustainable harvesting techniques like uprooting whole plants and cutting main roots. Hence, the need to document such indigenous knowledge before being lost for community usage and scientific validation.

Medically important bacteria isolated from commercial herbal medicines in Kampala city indicate the need to enhance safety frameworks.

The high global bacterial infection burden has created need to investigate the neglected potential drivers of pathogenic bacteria, to inform disease prevention. Kampala is facing a proliferation of herbalists, selling herbal medicine (HM), of largely unregulated microbiological quality. We evaluated the bacterial contamination burden in HM sold in Kampala, to support evidence-based redress. The total viable loads (TVL), total coliform counts (TCC), E. coli counts, and prevalence of selected bacterial strains in 140 HM were examined using conventional culture, following the guidelines of World Health Organization (WHO), and Uganda National Drug Authority (NDA). Data were analyzed using D'Agostino-Pearson test, frequencies, proportions, Chi-square, and Mann-Whitney U test with STATA version-15.0. Fifty (35.7%), fifty-nine (42.1%), and twelve (8.6%) HM were unsafe for human use because they exceeded WHO's permissible limits for TVL, TCC, and E. coli counts respectively. Solids had significantly higher mean TVL than liquids. Violation of NDA's guidelines was significantly associated with high TVL. Fifty-nine bacteria, viz., Klebsiella pneumoniae (n = 34; 57.6%), Escherichia. coli (12; 20.3%), Staphylococcus aureus (7; 11.9%), Klebsiella oxytoca (3; 5.1%), Bacillus cereus, Pseudomonas aeruginosa, and Enterobacter spp. (1; 1.7% each), were isolated from 45 (32.1%) samples. These bacteria can cause severe clinical diseases, and promote deterioration of HM potency.

Cytotoxicity of Medicinal Plant Species Used by Traditional Healers in Treating People Suffering From HIV/AIDS in Uganda.

Introduction: Many people living with HIV/AIDS (PLHIV) in Uganda widely use herbal medicines. However, their toxicity and safety have not been investigated. The use of these plants can potentially cause harmful effects to the health of patients. The purpose of this study was to determine the cytotoxicity of some commonly used medicinal plant species used by PLHIV. Methods: The cytotoxicity of the plant extracts was determined with the AlamarBlue cell viability assay using the human glioblastoma cell line U87.CD4.CXCR4. The cells were treated with varying concentrations of extracts of Warburgia ugandensis, Erythrina abyssinica, Cryptolepis sanguinolenta, Albizia coriaria, Psorospermum febrifugium, Gymnosporia senegalensis, Zanthoxylum chalybeum, Securidaca longipendunculata, Vachellia hockii, Gardenia ternifolia, and Bridelia micrantha reconstituted with ethanol and dimethyl sulfoxide (DMSO). Using regression analysis, the half maximal cytotoxic concentration (CC50) of the plant extracts were calculated from exponential curve fits, since they provided the highest coefficient of determination, R2. Results: The ethanol extracts of W. ugandensis (CC50 = 7.6 µg/ml) and A. coriaria (CC50 = 1.5 µg/ml) as well as the DMSO-reconstituted extracts of W. ugandensis (CC50 = 6.4 µg/ml) and A. coriria (CC50 = < 4 µg/ml) were highly cytotoxic. The cytotoxicity of W. ugandensis and A. coriaria compared well with the indigenous traditional knowledge of the toxic effects experienced when the plants were not used correctly. However, the cytotoxicity of most of the plant extracts (15/22) was low to moderate (CC50 = 21-200 µg/ml). Conclusion: Most of the plant species tested in this study had low to moderate cytotoxicity against U87.CD4.CXCR4 cells, except W. ugandensis and A. coriria which were highly cytotoxic.

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.

Antibiotic-resistance in medically important bacteria isolated from commercial herbal medicines in Africa from 2000 to 2021: a systematic review and meta-analysis.

BACKGROUND: Antimicrobial resistance is swiftly increasing all over the world. In Africa, it manifests more in pathogenic bacteria in form of antibiotic resistance (ABR). On this continent, bacterial contamination of commonly used herbal medicine (HM) is on the increase, but information about antimicrobial resistance in these contaminants is limited due to fragmented studies. Here, we analyzed research that characterized ABR in pathogenic bacteria isolated from HM in Africa since 2000; to generate a comprehensive understanding of the drug-resistant bacterial contamination burden in this region. METHODS: The study was conducted according to standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We searched for articles from 12 databases. These were: PubMed, Science Direct, Scifinder scholar, Google scholar, HerbMed, Medline, EMBASE, Cochrane Library, International Pharmaceutical Abstracts, Commonwealth Agricultural Bureau Abstracts, African Journal Online, and Biological Abstracts. Prevalence and ABR traits of bacterial isolates, Cochran's Q test, and the I2 statistic for heterogeneity were evaluated using MedCalcs software. A random-effects model was used to determine the pooled prevalence of ABR traits. The potential sources of heterogeneity were examined through sensitivity analysis, subgroup analysis, and meta-regression at a 95% level of significance. FINDINGS: Eighteen studies met our inclusion criteria. The pooled prevalence of bacterial resistance to at least one conventional drug was 86.51% (95% CI = 61.247-99.357%). The studies were highly heterogeneous (I2 = 99.17%; p < 0.0001), with no evidence of publication bias. The most prevalent multidrug-resistant species was Escherichia coli (24.0%). The most highly resisted drug was Ceftazidime with a pooled prevalence of 95.10% (95% CI = 78.51-99.87%), while the drug-class was 3rd generation cephalosporins; 91.64% (95% CI = 78.64-96.73%). None of the eligible studies tested isolates for Carbapenem resistance. Extended Spectrum ß-lactamase genes were detected in 89 (37.2%) isolates, mostly Salmonella spp., Proteus vulgaris, and K. pneumonia. Resistance plasmids were found in 6 (5.8%) isolates; the heaviest plasmid weighed 23,130 Kilobases, and Proteus vulgaris harbored the majority (n = 5; 83.3%). CONCLUSIONS: Herbal medicines in Africa harbor bacterial contaminants which are highly resistant to conventional medicines. This points to a potential treatment failure when these contaminants are involved in diseases causation. More research on this subject is recommended, to fill the evidence gaps and support the formation of collaborative quality control mechanisms for the herbal medicine industry in Africa.

Herbal medicine used for the treatment of diarrhea and cough in Kampala city, Uganda.

BACKGROUND: Globally, diarrheal and respiratory diseases are among the main causes of mortality and morbidity. In Uganda, cities are facing proliferation of trade in herbal medicines (HM), including those for diarrhea and/or cough. Information on the economic, and the ethnopharmacological aspects of these HM is scarce, deterring the sector from achieving optimal capacity to support national development. We profiled the anti-diarrhea and/or anti-cough HM, and the basic economic aspects of HM trade in Kampala city, to support ethnopharmacological knowledge conservation and strategic planning. METHODS: A cross-sectional survey was conducted on 65 herbalists using semi-structured questionnaires. This was supplemented by an observational survey using a high-resolution digital camera. Data were collected following the guidelines for research on HM, established by Uganda National Drug Authority, and World Health organization. RESULTS: Eighty-four plant species from 41 families were documented. Fabaceae and Myricaceae had the highest number of species (9, 10.7% each). Citrus limon (L.) Osbeck was the most commonly cited for cough, with a relative frequency of citation (RFC) of 1.00, and its relative medical importance was not significantly different from the other top 5 species except for Azadirachta indica A.Juss (RFC = 0.87). Entada abyssinica A. Rich (RFC = 0.97) was the most cited for diarrhea. Trees (34, 40.5%) were mostly used, and mainly harvested from wild habitats (55.2%) in 20 districts across Uganda. These HM were mainly sold as powders and concoctions, in markets, shops, pharmacies, and roadside or mobile stalls. The highest prices were Uganda Shillings (UGX) 48,000 ($13.15)/kg for Allium sativum L, and UGX 16,000 ($4.38)/kg for C. limon. All participants used HM trade as a sole source of basic needs; majority (60.0%) earned net monthly profit of UGX. 730,000 ($200) ≤ 1,460,000 ($400). The main hindrances to HM trade were the; disruptions caused by the COVID-19 pandemic (n = 65, 100%), and the scarcity of medicinal plants (58, 89.2%). CONCLUSION: There is a rich diversity of medicinal plant species traded in Kampala to treat diarrhea and cough. The HM trade significantly contributes to the livelihoods of the traders in Kampala, as well as the different actors along the HM value chain throughout the country.

African and Asian Medicinal Plants as a Repository for Prospective Antiviral Metabolites Against HIV-1 and SARS CoV-2: A Mini Review.

Introduction: The worldwide burden of viral infections has triggered a resurgence in the search for new and more efficient antiviral drugs. Scientists are also repurposing existing natural compounds such as the antimalarial drug artemisinin from Artemesia annua L. as potential drug candidates for some of the emerging and re-emerging viral infections such as covid-19 Aim: The aim of this review was to analyse the existing literature to explore the actual or potential natural antiviral compounds from African and Asian medicinal plants as lead compounds in the drug discovery process. Methods: We searched the literature on African and Asian medicinal plant species as antiviral agents for HIV-1 and the novel coronavirus (SARS-CoV-2) in various databases and search engines such as Web of Science, Google Scholar and PubMed. The search was limited to in vitro, in vivo, and clinical studies and excluded in silico studies. Results: We present 16 plant species with actual or potential antiviral activity against HIV-1 and SARS-CoV-2. These plant species span the continents of Africa and Asia where they are widely used for treating several other ailments. Conclusion: Natural compounds from plants can play a significant role in the clinical management of HIV/AIDS and the covid-19 pandemic. More research needs to be conducted to investigate the potential toxicities of the various compounds and their efficacies in clinical settings.

Pharmacological Assessment of the Antiprotozoal Activity, Cytotoxicity and Genotoxicity of Medicinal Plants Used in the Treatment of Malaria in the Greater Mpigi Region in Uganda.

We investigated the potential antimalarial and toxicological effects of 16 medicinal plants frequently used by traditional healers to treat malaria, fever, and related disorders in the Greater Mpigi region in Uganda. Species studied were Albizia coriaria, Cassine buchananii, Combretum molle, Erythrina abyssinica, Ficus saussureana, Harungana madagascariensis, Leucas calostachys, Microgramma lycopodioides, Morella kandtiana, Plectranthus hadiensis, Securidaca longipedunculata, Sesamum calycinum subsp. angustifolium, Solanum aculeastrum, Toddalia asiatica, Warburgia ugandensis, and Zanthoxylum chalybeum. In addition, the traditional healers indicated that P. hadiensis is used as a ritual plant to boost fertility and prepare young women and teenagers for motherhood in some Ugandan communities where a high incidence of rapidly growing large breast masses in young female patients was observed (not necessarily breast cancer). We present results from various in vitro experiments performed with 56 different plant extracts, namely, 1) an initial assessment of the 16 species regarding their traditional use in the treatment of malaria by identifying promising plant extract candidates using a heme biocrystallization inhibition library screen; 2) follow-up investigations of antiprotozoal effects of the most bioactive crude extracts against chloroquine-resistant P. falciparum K1; 3) a cytotoxicity counterscreen against human MRC-5SV2 lung fibroblasts; 4) a genotoxicity evaluation of the extract library without and with metabolic bioactivation with human S9 liver fraction; and 5) an assessment of the mutagenicity of the ritual plant P. hadiensis. A total of seven extracts from five plant species were selected for antiplasmodial follow-up investigations based on their hemozoin formation inhibition activity in the heme biocrystallization assay. Among other extracts, an ethyl acetate extract of L. calostachys leaves exhibited antiplasmodial activity against P. falciparum K1 (IC50 value: 5.7 µg/ml), which was further characterized with a selectivity index of 2.6 (CC50 value: 14.7 µg/ml). The experiments for assessment of potential procarcinogenic properties of plant extracts via evaluation of in vitro mutagenicity and genotoxicity indicated that few extracts cause mutations. The species T. asiatica showed the most significant genotoxic effects on both bacterial test strains (without metabolic bioactivation at a concentration of 500 µg/plate). However, none of the mutagenic extracts from the experiments without metabolic bioactivation retained their genotoxic activity after metabolic bioactivation of the plant extract library through pre-incubation with human S9 liver fraction. While this study did not show that P. hadiensis has genotoxic properties, it did provide early stage support for the therapeutic use of the medicinal plants from the Greater Mpigi region.

In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion.

BACKGROUND: In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation. METHODS: Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated. RESULTS: Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 µg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups. CONCLUSION: A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.

Antiinflammatory Medicinal Plants from the Ugandan Greater Mpigi Region Act as Potent Inhibitors in the COX-2/PGH2 Pathway.

Our study investigates 16 medicinal plants via assessment of inhibition of proinflammatory enzymes such as cyclooxygenases (COX). The plants are used by traditional healers in the Greater Mpigi region in Uganda to treat inflammation and related disorders. We present results of diverse in vitro experiments performed with 76 different plant extracts, namely, (1) selective COX-2 and COX-1 inhibitor screening; (2) 15-LOX inhibition screening; (3) antibacterial resazurin assay against multidrug-resistant Staphylococcus aureus, Listeria innocua, Listeria monocytogenes, and Escherichia coli K12; (4) DPPH assay for antioxidant activity; and (5) determination of the total phenolic content (TPC). Results showed a high correlation between traditional use and pharmacological activity, e.g., extracts of 15 out of the 16 plant species displayed significant selective COX-2 inhibition activity in the PGH2 pathway. The most active COX-2 inhibitors (IC50 < 20 µg/mL) were nine extracts from Leucas calostachys, Solanum aculeastrum, Sesamum calycinum subsp. angustifolium, Plectranthus hadiensis, Morella kandtiana, Zanthoxylum chalybeum, and Warburgia ugandensis. There was no counteractivity between COX-2 and 15-LOX inhibition in these nine extracts. The ethyl acetate extract of Leucas calostachys showed the lowest IC50 value with 0.66 µg/mL (COX-2), as well as the most promising selectivity ratio with 0.1 (COX-2/COX-1). The TPCs and the EC50 values for DPPH radical scavenging activity showed no correlation with COX-2 inhibitory activity. This led to the assumption that the mechanisms of action are most likely not based on scavenging of reactive oxygen species and antioxidant activities. The diethyl ether extract of Harungana madagascariensis stem bark displayed the highest growth inhibition activity against S. aureus (MIC value: 13 µg/mL), L. innocua (MIC value: 40 µg/mL), and L. monocytogenes (MIC value: 150 µg/mL). This study provides further evidence for the therapeutic use of the previously identified plants used medicinally in the Greater Mpigi region.