Ethnomedicinal uses, biological activities, phytochemistry and conservation of African ginger (Siphonochilus aethiopicus): A commercially important and endangered medicinal plant.

ETHNOPHARMACOLOGICAL RELEVANCE: In sub-Saharan Africa, African ginger (Siphonochilus aethiopicus) is used for treating common illnesses including colds, coughs, inflammation and related symptoms. The available literature survey on this plant provided scarce anecdotal information, particularly in western and eastern Africa, with a few reports on its bioactivity. In addition, the indigenous knowledge and conservation strategies of this economically important and critically endangered species are currently fragmented. AIM OF THE REVIEW: This review entails a critical appraisal of existing literature on the ethnomedicinal uses, biological activities, phytochemicals, research opportunities and prospects for the sustainable use of S. aethiopicus. MATERIALS AND METHODS: This review was conducted using a comprehensive literature search on the ethnomedicinal uses, biological activities and phytochemistry of S. aethiopicus throughout its distributional range. The conservation status and associated bio-economy potential of African ginger were also assessed. We searched different online databases (e.g. Google Scholar, ScienceDirect, PubMed and Scopus) for peer-reviewed journals, conference outputs, international, regional and national organizational reports, published books and theses. RESULTS: We established that S. aethiopicus is used to treat a wide variety of ailments such as respiratory problems (including cough, influenza), pain, inflammation and malaria. Extracts of African ginger are used as an ingredient in some commercialised products for nutraceutical, cosmeceutical and pharmaceutical purposes. The rhizome extract demonstrated anti-asthmatic, anti-inflammatory, and antiplasmodial activities, which led to the development of a patented novel extract for treating asthma and allergies. Phytochemical analysis of leaf, root and rhizome extracts of African ginger revealed the presence of flavonoids, phenolic acids, volatile and essential oils as the major constituents. These phytochemicals are known to possess bioactivities such as antimicrobial and anti-inflammatory activities. Particularly, the bioactive compounds, siphonochilone and eucalyptol, found in the roots and rhizomes have demonstrated potential to be used in remedies for treating asthma and allergic reactions. Furthermore, extracts of S. aethiopicus contained natural anti-inflammatory mediators with potential to combat and manage chronic inflammation. This plant is classified on the Red List of South African Plants as a critically endangered plant. Its high risk of extinction due to its unsustainable harvesting and exploitation necessitates its rapid propagation and cultivation to meet its increasing demand. CONCLUSIONS: The review highlights the therapeutic potential of S. aethiopicus and rational prioritization of this plant species with the potential for isolating new bioactive compounds. In the light of the use of this plant extract in traditional medicine and many commercial products, there is a heightened need to explore the mechanism(s) of action of the identified extracts and bioactive compounds in order to fully understand their pharmacokinetics and probably elucidate the pathways of their activities.

Grewia mollis Leaf Extracts and Fractions Demonstrated Good Inhibitory Activity on Pro-Inflammatory Enzymes and with Lower Cytotoxicity in vitro.

INTRODUCTION: Plant extracts are used to treat illnesses, promote health, and maintain general well-being in traditional medicine. Grewia mollis Juss (Malvaceae) is one of the medicinal herbs that is used traditionally to treat chronic diseases and related pain because currently used anti-inflammatory drugs may cause severe side effects, and naturally occurring compounds with reduced cytotoxicity could be explored for therapeutic goals. MATERIALS AND METHODS: Dried leaf of G. mollis was extracted with aqueous and organic solvents and partitioned based on polarity using solvent-solvent methods. The extracts were tested in anti-inflammatory assays against cyclooxygenases and lipoxygenase, and the safety profile was determined in a cell-based in-vitro assay. RESULTS: The n-hexane fraction of G. mollis leaf extracts had significant activity against both COX-1 (IC50 =0.97±1.9 µg/mL) and COX-2 (IC50 =1.13±0.2 µg/mL) better than the indomethacin positive control (IC50 =1.3±0.6 and 1.52±0.2 µg/mL), respectively (p≤ 0.05). Also, all the extracts and fractions of G. mollis tested inhibited the activity of 15-LOX (IC50 =12.48±2.9 to 29.43±9.9 µg/mL) better than the quercetin reference control (IC50 =61.82±5.5 µg/mL), with the butanol fraction demonstrating the best anti-15 LOX action (IC50 =12.48±2.9 µg/mL). Furthermore, all the extracts and fractions of G. mollis had relatively lower cytotoxicity on vero monkey kidney cells (LD50 =30.56-479±0.07 µg/mL) compared to the doxorubicin positive control (LD50 =2.59 µg/mL), but the selectivity index (SI=1.04-1.89) determination suggested that some of the extracts may contain toxic constituents. CONCLUSION: Organic extracts of the leaves of Grewia mollis contained bioactive molecules with potent action on COX-2 and 15-LOX. Targeted high-resolution high-performance liquid chromatographic (HPLC) methods have streamlined and enhanced bioactive compound isolation and purification process. This allows for the separation of undesirable compounds that could cause metabolic cytotoxicity in the plant extract mixtures. The method could be used to develop an alternative therapeutic strategy to manage pain associated with chronic inflammation where the use of NSAID is problematic.

Investigation of the Mechanism of Anti-Inflammatory Action and Cytotoxicity of a Semipurified Fraction and Isolated Compounds From the Leaf of Peltophorum africanum (Fabaceae).

Peltophorum africanum extracts have been shown to possess many important medicinal benefits, including anti-inflammatory and antiviral activities. However, the mechanism of action is poorly understood. The mechanism of anti-inflammatory action was determined by measuring the synthesis of cytokines in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage cells in vitro. Compound 1 (CP1), compound 2 (CP2), and fraction F3.3.0 (F3.3.0) significantly reduced the synthesis of interleukin 1ß (IL-1ß) from RAW 264.7 cells (1.18, 1.32, and 0.92 ng/mL), respectively. Similarly, CP1, CP2, and F3.3.0 inhibited the production of IL-2 and tumor necrosis factor-α (TNF-α) by RAW 264.7 cells (0.41, 0.60, 0.74 and 0.11, 0.27, 0.24 ng/mL, respectively. In addition, CP1 and CP2 had lower cytotoxicity toward RAW 264.7 cells, with CP2 indicating the lowest cytotoxicity (LD50 = 207.88 µg/mL). The mechanism of action was found to be via the inhibition of pro-inflammation cytokines (IL-1 ß and TNF-α). This observation may support the use of P africanum to treat pain-related conditions.

First isolation of glutinol and a bioactive fraction with good anti-inflammatory activity from n-hexane fraction of Peltophorum africanum leaf.

OBJECTIVE: To investigate the anti-inflammatory activity of different fractions and glutinol (isolated compound), using nitric oxide synthase and cyclooxygenase (COX) inhibition as an indication of anti-inflammatory activity. METHODS: Anti-inflammatory activity was evaluated using an in vitro assay determining the inhibition of the activity of pro-inflammatory enzyme model. Cyclooxygenases and inducible nitric oxide synthase are crucial enzymes involved in the pathogenesis of many chronic inflammatory conditions. RESULTS: Sub-fraction F3.3 that was derived from n-hexane fraction of PA leaves significantly inhibited (P = 0.01) the catalytic activity of COX-2 (IC50 = 0.67 µg/mL) better than isolated compound, glutinol (IC50 = 1.22 µg/mL), compound 2 (CP2) (IC50 = 1.71 µg/mL) and sub-fraction F3.3.0 (IC50 = 1.30 µg/mL). A similar trend was observed in investigation of the inhibition of nitric oxide synthesis in RAW 264.7 cells by F3.3, glutinol, CP2 and F3.3.0. Inducible COX-2 and inducible nitric oxide synthase are among potent signalling enzymes that exacerbate inflammation. CONCLUSIONS: Bioactive sub-fractions (F3.3 and F3.3.0) derived from the n-hexane fraction of PA had good anti-inflammatory activity, and the isolated compound, and glutinol may be useful as a template for the development of new anti-inflammatory drugs.

The anti-inflammatory and antioxidant activity of 25 plant species used traditionally to treat pain in southern African.

BACKGROUND: Inflammation is a common risk factor in the pathogenesis of conditions such as infections, arthritis, type 2 diabetes mellitus, obesity and cancer. An ethnobotanical survey of medicinal plants used traditionally to treat inflammation and related disorders such as pain, arthritis and stomach aches in southern Africa led to the selection of 25 plant species used in this study. METHODS: The antioxidant activities of acetone extracts were determined by measuring the free radical scavenging activity and ferric reducing ability, respectively. The anti-inflammatory activities of the extracts were determined by measuring the inhibitory effect of the extracts on the activities of the pro-inflammatory enzyme, lipoxygenase and inducible nitric oxide synthase. RESULTS: Extracts of Peltophorum africanum had good antioxidant activity with IC50 values of 4.67 ± 0.31 µg/mL and 7.71 ± 0.36 µg/mL compared to that of the positive control ascorbic acid (2.92 ± 0.14 µg/mL and 13.57 ± 0.44 µg/mL), using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods, respectively. The metabolism of linoleic acid to leukotriene derivatives by 15-lipoxygenase (15-LOX) was also inhibited by the crude acetone extracts of Peltophorum africanum (IC50 = 12.42 µg/mL), Zanthoxylum capense (IC50 = 14.92 µg/mL) compared to the positive control quercetin (IC50 = 8.75 µg/mL). There was a poor correlation between the flavonoid content and 15-LOX inhibition by the extracts (R(2) = 0.05), indicating that flavonoids are not involved in LOX inhibition. Extracts of Clausena anisata, at a concentration of 6.25 µg/mL inhibited nitric oxide production by RAW 264.7 macrophage cell lines in vitro by 96 %. The extracts of Zanthoxylum capense were the least cytotoxic (IC50 > 1000 µg/mL) when the extract toxicity was determined against Vero (African green Monkey) kidney cell lines. CONCLUSION: Some plant species used traditionally to treat pain have reasonable anti-inflammatory activity and flavonoids are probably not involved in this process.