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.

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.