Plant-derived sulfur containing natural products produced as a response to biotic and abiotic stresses: A review of their structural diversity and medicinal importance

Plant-derived sulfur-containing secondary metabolites constitute a small group of low-molecular weight natural products, which play a vital role in plant-pest interactions in numerous plant families andrepresent major defense molecules in the Asteraceae, Alliaceae, and Brassicaceae families. In this review we highlight the crucial role of environmental stress factors in the production of S-containing secondary metabolites. Furthermore, we describe a serendipitous variety of plant-derived sulfur-containing natural products produced or induced under biotic and abiotic stress and their structural diversity, promising pharmacological properties for use by humans, and beneficial effects for plants. Specifically, cruciferous phytoalexins are known as elicit plant defense molecules. Glucosinolates are candidates for tumorpreventive effects. Cysteine sulfoxides found in garlic are considered as profound antimicrobial agents. In this review, we discuss types of S bonds in the molecules and their relevance for the medicinal effect as well as the biological activities of sulfur-containing secondary metabolites and possible future avenues

FLAVONOIDS FROM SUDANESE ALBIZIA ZYGIA (LEGUMINOSAE, SUBFAMILY MIMO-SOIDEAE), A PLANT WITH ANTIMALARIAL POTENCY

Three flavonoids were isolated for the first time from the Sudanese medicinal plants Albizia zygia. Compounds 1-3 were identified by interpretation of ESI mass data, 1H, 13C and 2D NMR as well as by comparison with published data as 4',7-dihydroxyflavanone (1) 3',4',7-trihydroxyflavone (2), 3-O-methylfisetin (3',4',7-trihydroxy-3-methoxyflavone, 3). All flavonoids were tested against Plasmodium falciparum, and only compound 2 showed high antimalarial activity (IC50 0.078 μg/ml)

Sulfur but not nitrogen supply increases the ITC/Nitrile ratio in Pak Choi (Brassica rapa subsp. chinensis (L.) Hanelt)

Glucosinolates (GLS) are a serendipitous class of secondary metabolites found in pak choi, a Chinese cabbage (Brassica rapa subsp. chinensis (L.) Hanelt). GLS are hydrolyzed by the enzyme myrosinase to obtain isothiocyanates (ITC), nitriles, and epithionitriles. GLS hydrolysis products (GLS-HP) are responsible for the typical flavor and odour of pak choi. Little is known about the influence of S and N interactions on pak choi GLS and their hydrolysis products (GLS-HP), especially nitriles.We investigated the effect of S and N concentrations on pak choi GLS, isothiocyanates, and nitriles content under varying nitrogen (0.75 and 1.5 g N pot–1) and sulfur (0, 0.06, and 0.3 g S pot–1) supply. Increasing the S supply but not N resulted in a reciprocal increase of the total GLS. The GLS concentration decreased under S deficiency. S supply delivered an optimized GLS pattern, and substantially enhanced the synthesis of aliphatic GLS and ITC in particular. In contrast, N-rich nutrition favored the synthesis of indolic GLS and nitriles, the latter are known to have less health beneficial potential and even showed harmful effects. The study indicates, for the first time, that the ITC/nitrile ratio increases under S supply.GLS and their GLS degradation products in pak choi showed a strong response to sulfur supply. Moreover, the ITC/nitrile ratio might be used as a physiological trait to compare nutritional quality and health benefits of brassica species

Regulation of Selenium/Sulfur Interactions to Enhance Chemopreventive Effects: Lessons to Learn from Brassicacrassiceae

Selenium (Se) is an essential trace element, which represents an integral part of glutathione peroxidase and other selenoproteins involved in the protection of cells against oxidative damage. Selenomethionine (SeMet), selenocysteine (SeCys), and methylselenocysteine (MeSeCys) are the forms of Se that occur in living systems. Se-containing compounds have been found to reduce carcinogenesis of animal models, and dietary supplemental Se might decrease cancer risk. Se is mainly taken up by plant roots in the form of selenate via high-affinity sulfate transporters. Consequently, owing to the chemical similarity between Se and sulfur (S), the availability of S plays a key role in Se accumulation owing to competition effects in absorption, translocation, and assimilation. Moreover, naturally occurring S-containing compounds have proven to exhibit anticancer potential, in addition to other bioactivities. Therefore, it is important to understand the interaction between Se and S, which depends on Se/S ratio in the plant or/and in the growth medium. Brassicaceae (also known as cabbage or mustard family) is an important family of flowering plants that are grown worldwide and have a vital role in agriculture and populations' health. In this review we discuss the distribution and further interactions between S and Se in Brassicaceae and provide several examples of Se or Se/S biofortifications' experiments in brassica vegetables that induced the chemopreventive effects of these crops by enhancing the production of Se- or/and S-containing natural compounds. Extensive further research is required to understand Se/S uptake, translocation, and assimilation and to investigate their potential role in producing anticancer drugs

Bioprospecting of South African plants as a unique resource for bioactive endophytic microbes

South Africa has a long history and strong belief in traditional herbal medicines. Using ethnobotanical knowledge as a lead, a large number of South African medicinal plants have been discovered to possess a wide spectrum of pharmacological properties. In this review, bioprospecting of endophytes is highlighted by following the advantages of the ethnomedicinal approach together with identifying unique medicinal plants where biological activity may be due to endophytes. This review focuses on the current status of South African medicinal plants to motivate the research community to harness the benefits of ethnobotanical knowledge to investigate the presence of endophyticmicrobes from the most potent South Africanmedicinal plants. The potential chemical diversity and subsequent putative medicinal value of endophytes is deserving of further research. A timely and comprehensive review of literature on recently isolated endophytes and their metabolites was conducted.Worldwide literature from the last 2 years demonstrating the importance of ethnobotanical knowledge as a useful approach to discover endophytic microbes was documented. Information was obtained from scientific databases such as Pubmed, Scopus, Scirus, Google Scholar, Dictionary of Natural Products, Chemical Abstracts Services, official websites, and scientific databases on ethnomedicines. Primary sources such as books, reports, dissertations, and thesises were accessed where available. Recently published information on isolated endophytes with promising bioactivity and their bioactive natural products worldwide (2015-2017) was summarized. The potential value of South African medicinal plants as sources of endophytes is discussed. The insights provided through this study indicate that medicinal plants in South Africa are highly under-investigated sources of potentially useful endophytic microbes. New approaches may be used by medicinal plant scientists for further exploration of natural products from endophytic fungi and bacteria in southern Africa.The University of Pretoria, South Africahttp://www.frontiersin.org/Pharmacologyam2019Paraclinical Science

Bioprospecting of South African plants as a unique resource for bioactive endophytic microbes

South Africa has a long history and strong belief in traditional herbal medicines. Using ethnobotanical knowledge as a lead, a large number of South African medicinal plants have been discovered to possess a wide spectrum of pharmacological properties. In this review, bioprospecting of endophytes is highlighted by following the advantages of the ethnomedicinal approach together with identifying unique medicinal plants where biological activity may be due to endophytes. This review focuses on the current status of South African medicinal plants to motivate the research community to harness the benefits of ethnobotanical knowledge to investigate the presence of endophyticmicrobes from the most potent South Africanmedicinal plants. The potential chemical diversity and subsequent putative medicinal value of endophytes is deserving of further research. A timely and comprehensive review of literature on recently isolated endophytes and their metabolites was conducted.Worldwide literature from the last 2 years demonstrating the importance of ethnobotanical knowledge as a useful approach to discover endophytic microbes was documented. Information was obtained from scientific databases such as Pubmed, Scopus, Scirus, Google Scholar, Dictionary of Natural Products, Chemical Abstracts Services, official websites, and scientific databases on ethnomedicines. Primary sources such as books, reports, dissertations, and thesises were accessed where available. Recently published information on isolated endophytes with promising bioactivity and their bioactive natural products worldwide (2015-2017) was summarized. The potential value of South African medicinal plants as sources of endophytes is discussed. The insights provided through this study indicate that medicinal plants in South Africa are highly under-investigated sources of potentially useful endophytic microbes. New approaches may be used by medicinal plant scientists for further exploration of natural products from endophytic fungi and bacteria in southern Africa.The University of Pretoria, South Africahttp://www.frontiersin.org/Pharmacologyam2019Paraclinical Science

Secondary Metabolite Profile and Pharmacological Opportunities of Lettuce Plants following Selenium and Sulfur Enhancement

Selenium (Se) is an essential trace nutrient for humans and animals owing to its role in redox regulation, thyroid hormone control factors, immunity, inflammatory reactions, brain activities, and carbohydrate regulation. It is also important to support muscle development, as well as for reproductive and cardiovascular well-being. Furthermore, sulfur is known to be a healing element, due to the remarkable function of specialized and secondary S-containing compounds. The scope of the current study was to determine the impact of Se and S enrichment on the secondary metabolite accumulation and antibacterial and NO inhibition activities in green and red leaf lettuce (V1 and V2, respectively) As with antibacterial activity, the acetone extract of green (V1) lettuce treated with adequate (S1) and higher S (S2) under Se-limiting conditions showed the ability to inhibit nitric oxide (NO) release from macrophages. NO production by macrophages was inhibited by 50% at respective concentrations of 106.1 ± 2.4 and 101.0 ± 0.6 μg/mL with no toxic effect on the cells, in response to S1 and S2, respectively, under Se-deficient conditions (Se0). Furthermore, the red cultivar (V2) exhibited the same effect as the green cultivar (V1) regarding NO inhibition, with IC50 = 113.0 ± 4.2 μg/mL, in response to S1/Se2 treatments. Collectively, the promising NO inhibitory effect and antibacterial activity of red lettuce under the above-mentioned conditions might be attributed to the production of flavonoid glycosides and phenylpropanoic acid esters under the same condition. To the best of our knowledge, this is the first report to show the novel approach of the NO inhibitory effect of Se and S enrichment in food crops, as an indicator for the potential of Se and S as natural anti-inflammatory agents

Comparative Metabolite Profile, Biological Activity and Overall Quality of Three Lettuce (Lactuca sativa L., Asteraceae) Cultivars in Response to Sulfur Nutrition

The main objective of the present study was to assess the effects of sulfur (S) nutrition on plant growth, overall quality, secondary metabolites, and antibacterial and radical scavenging activities of hydroponically grown lettuce cultivars. Three lettuce cultivars, namely, Pazmanea RZ (green butterhead, V1), Hawking RZ (green multi-leaf lettuce, V2), and Barlach RZ (red multi-leaf, V3) were subjected to two S-treatments in the form of magnesium sulfate (+S) or magnesium chloride (−S). Significant differences were observed under −S treatments, especially among V1 and V2 lettuce cultivars. These responses were reflected in the yield, levels of macro- and micro-nutrients, water-soluble sugars, and free inorganic anions. In comparison with the green cultivars (V1 and V2), the red-V3 cultivar revealed a greater acclimation to S starvation, as evidenced by relative higher plant growth. In contrast, the green cultivars showed higher capabilities in production and superior quality attributes under +S condition. As for secondary metabolites, sixteen compounds (e.g., sesquiterpene lactones, caffeoyl derivatives, caffeic acid hexose, 5-caffeoylquinic acid (5-OCQA), quercetin and luteolin glucoside derivatives) were annotated in all three cultivars with the aid of HPLC-DAD-MS-based untargeted metabolomics. Sesquiterpene lactone lactucin and anthocyanin cyanidin 3-O-galactoside were only detected in V1 and V3 cultivars, respectively. Based on the analyses, the V3 cultivar was the most potent radical scavenger, while V1 and V2 cultivars exhibited antibacterial activity against Staphylococcus aureus in response to S provision. Our study emphasizes the critical role of S nutrition in plant growth, acclimation, and nutritional quality. The judicious-S application can be adopted as a promising antimicrobial prototype for medical applications

Selenium Enrichment of Green and Red Lettuce and the Induction of Radical Scavenging Potential

Selenium (Se)-enriched vegetables are promising dietary sources of Se, which provides beneficial biological effects in humans. In this study, we investigated the effects of foliar application of Se on hydroponically grown multi-leaf green (V1) and red (V2) lettuce plants. Three selenate (SeIV) amendment levels were evaluated for their influence on plant growth, elemental composition and radical scavenging capacity. Lettuce heads biofortified with 0.598 mg Se plant−1 accumulated 19.6–23.6 and 14.9–17.6 μg Se g−1 DM in the multi-leaf green (V1) and red (V2) lettuce plants, respectively. The accumulated Se levels can contribute significantly to the recommended dietary allowance of 70 µg day−1 for adult men and 60 µg day−1 for adult women. Accordingly, both V1 and V2 lettuce cultivars grown under the Se3 foliar application condition can cover the daily requirement for adult men by approximately 100% and 85% to 100%, respectively, by consuming 75–90 g or 100 g fresh weight from V1 or V2, respectively. The ABTS radical scavenging potential of green lettuce was induced at Se2 and Se3 foliar application levels, where the IC50 was 1.124 ± 0.09 μg mL−1 at Se0 and improved to 0.795 ± 0.03 and 0.697 ± 0.01 μg mL−1, respectively. There was no cytotoxicity against Vero kidney cells among all treated lettuce plants at the highest concentration tested of 1 mg/mL. Finally, a further focused investigation of the metabolic profile of lettuce plants under varied Se levels needs to be investigated in future studie

Anti-inflammatory and antioxidant properties of leaf extracts of eleven South African medicinal plants used traditionally to treat inflammation

ETHNOPHARMACOLOGICAL RELEVANCE : Inflammation is a complex mechanism employed by the body to promote healing and restoration to normal function in the event of injury. Eleven plant species were selected in this study based on their use in traditional medicine against inflammation in South Africa. METHODS : Hexane, acetone, ethanol, methanol and water extracts of the powdered plants were prepared and a total of fifty-five extracts were tested for their anti-inflammatory and antioxidant activities. The anti-inflammatory activity of extracts was evaluated via the 15-lipoxygenase (15-LOX) inhibitory and the nitric oxide (NO) inhibition assays using lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophages. Total flavonoid and total phenolic contents were determined. The antioxidant activity of the extracts was performed using radical scavenging DPPH (2, 2-diphenyl-1-picrylhydrazyl) and electron reducing ABTS (2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays. RESULTS : The hexane extract of Typha capensis (TC) had good lipoxygenase inhibitory activity with IC50 of 4.65 µg/mL, significantly (p < 0.05) higher than that of the positive control quercetin (IC50 = 24.60). The same extract also had good nitric oxide inhibitory activity with 86% NO inhibition and cell viability of 97% at 50 µg/mL. The TC acetone extract had the best antioxidant activity with IC50 of 7.11 and 1.91 µg/mL respectively in the DPPH and ABTS assays. Following fractionation of the TC plant material, the ethyl acetate fraction had interesting antioxidant activity and the methanol/water (35%) and hexane fractions had good 15-LOX inhibitory activity. The antioxidant and anti-inflammatory activities therefore resided in both polar and more non-polar fractions. CONCLUSION : The acetone extract of Typha capensis and its fractions had good anti-inflammatory and antioxidant activities, supporting the medicinal use of this species against inflammation. Other species including Ficus elastica, Carpobrotus edulis, Cotyledon orbiculata and Senna italica also had good activity worthy of further investigation.The National Research Foundation , South Africa (grant number 105993 ) is thanked for providing research funding. The NRF and University of Pretoria , South Africa are acknowledged for doctoral fellowships to OM.http://www.elsevier.com/locate/jethpharm2020-04-24hj2019Paraclinical Science