Saponins: From Diversity to Structural Modification and Bioactive Responses in Model Systems

Pro-inflammatory cytokines and anti-inflammatory cytokines are important mediators that regulate the inflammatory response in inflammation-related diseases. The aim of this study is to evaluate different New Zealand (NZ)-grown ginseng fractions on the productions of pro-inflammatory and anti-inflammatory cytokines in human monocytic THP-1 cells. Four NZ-grown ginseng fractions, including total ginseng extract (TGE), non-ginsenoside fraction extract (NGE), high-polar ginsenoside fraction extract (HPG), and less-polar ginsenoside fraction extract (LPG), were prepared and the ginsenoside compositions of extracts were analyzed by HPLC using 19 ginsenoside reference standards. The THP-1 cells were pre-treated with different concentrations of TGE, NGE, HPG, and LPG, and were then stimulated with lipopolysaccharide (LPS). The levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and anti-inflammatory cytokines, such as interleukin-10 (IL-10), and transforming growth factor beta-1 (TGF-β1), were determined by enzyme-linked immunosorbent assay (ELISA). TGE at 400 µg/mL significantly inhibited LPS-induced TNF-α and IL-6 productions. NGE did not show any effects on inflammatory secretion except inhibited IL-6 production at a high dose. Furthermore, LPG displayed a stronger effect than HPG on inhibiting pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) productions. Particularly, 100 µg/mL LPG not only significantly inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, but also remarkably enhanced the production of anti-inflammatory cytokine IL-10. NZ-grown ginseng exhibited anti-inflammatory effects in vitro, which is mainly attributed to ginsenoside fractions (particularly less-polar ginsenosides) rather than non-saponin fractions. Full article

Sea cucumbers are slow-moving organisms that use morphological, but also a diverse combination of chemical defenses to improve their overall fitness and chances of survival. Since chemical defense compounds are also of great pharmaceutical interest, we pinpoint the importance of biological screenings that are a relatively fast, informative and inexpensive way to identify the most bioactive organisms prior to further costly and elaborate pharmacological screenings. In this study, we investigated the presence and absence of chemical defenses of 14 different sea cucumber species from three families (Holothuriidae, Stichopodidae and Synaptidae) against ecological factors such as predation and pathogenic attacks. We used the different sea cucumber crude extracts as well as purified fractions and pure saponin compounds in a portfolio of ecological activity tests including fish feeding assays, cytotoxicity tests and antimicrobial assays against environmental pathogenic and non-pathogenic bacteria. Furthermore, we quantified and correlated the concentrations of sea cucumber characteristic saponin compounds as effective chemical defensive compounds in all 14 crude extracts by using the vanillin–sulfuric acid test. The initial results revealed that among all tested sea cucumber species that were defended against at least one ecological threat (predation and/or bacterial attack), Bohadschiaargus, Stichopuscholoronotus and Holothuria fuscopunctata were the three most promising bioactive sea cucumber species. Therefore, following further fractionation and purification attempts, we also tested saponin-containing butanol fractions of the latter, as well as two purified saponin species from B. argus. We could demonstrate that both, the amount of saponin compounds and their structure likely play a significant role in the chemical defense strategy of the sea cucumbers. Our study concludes that the chemical and morphological defense mechanisms (and combinations thereof) differ among the ecological strategies of the investigated holothurian species in order to increase their general fitness and level of survival. Finally, our observations and experiments on the chemical ecology of marine organisms can not only lead to a better understanding of their ecology and environmental roles but also can help in the better selection of bioactive organisms/compounds for the discovery of novel, pharmacologically active secondary metabolites in the near future. Full article

The target diosgenin–betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC₅₀ = 6.5 ± 1.1 µM), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds. Full article

Panax vietnamensis (PV), a wild Panax species discovered in Vietnam in 1973, has been increasingly overexploited due to its economic value and therapeutic uses. This resulted in the development of PV cultivation to meet the market demand. There is little information on the accumulation of saponins in PV during cultivation, but this information could serve as an indication of the appropriate harvest time. In this study we developed an HPLC-UV/ELSD method to simultaneously determine the content of 10 characteristic saponins in PV from 2–7 years old, including G-Rb1, G-Rd, G-Rg1, G-Re, N-R1, M-R1, M-R2, V-R2, V-R11, and p-RT4. The result indicated that from 2 to 5 years, the content of saponins in PV rhizome and radix increase 3.02 and 4.2 times, respectively, whereas from 5 to 7 years, no significant changes were observed. Hence, our study suggests that after 5 years of growth could be considered as an appropriate time for PV to be harvested. Among the analyzed saponins, G-Rg1, G-Rb1, G-Rd, and especially M-R2 were the major saponins that contributed to the change of PV’s saponin content through the years. In addition, the developed and validated HPLC method was proven to be reliable and effective for quality control of PV. Full article

Ginseng is an increasingly popular ingredient in supplements for healthcare products and traditional medicine. Heat-processed ginsengs, such as red ginseng or black ginseng, are regarded as more valuable for medicinal use when compared to white ginseng due to some unique less polar ginsenosides that are produced during heat-treatment. Although ginseng leaf contains abundant ginsenosides, attention has mostly focused on ginseng root; relatively few publications have focused on ginseng leaf. Raw ginseng leaf was steamed nine times to make black ginseng leaf using a process that is similar to that used to produce black ginseng root. Sixteen ginsenosides were analyzed during each steaming while using high-performance liquid chromatography (HPLC). The contents of ginsenosides Rd and Re decreased and the less polar ginsenosides (F2, Rg3, Rk2, Rk3, Rh3, Rh4, and protopanaxatriol) enriched during steam treatment. After nine cycles of steaming, the contents of the less polar ginsenosides F2, Rg3, and Rk2 increased by 12.9-fold, 8.6-fold, and 2.6-fold, respectively. Further, we found that the polar protopanaxadiol (PPD) -type ginsenosides are more likely to be converted from ginsenoside Rg3 to ginsenosides Rk1 and Rg5 via dehydration from Rg3, and from ginsenoside Rh2 to ginsenosides Rk2 and Rh3 through losing an H₂O molecule than to be completely degraded to the aglycones PPD during the heat process. This study suggests that ginseng leaves can be used to produce less polar ginsenosides through heat processes, such as steaming. Full article

Saponins are amphiphilic molecules consisting of carbohydrate and either triterpenoid or steroid aglycone moieties and are noted for their multiple biological activities—Fungicidal, antimicrobial, antiviral, anti-inflammatory, anticancer, antioxidant and immunomodulatory effects have all been observed. Saponins from natural sources have long been used in herbal and traditional medicines; however, the isolation of complexed saponins from nature is difficult and laborious, due to the scarce amount and structure heterogeneity. Chemical synthesis is considered a powerful tool to expand the structural diversity of saponin, leading to the discovery of promising compounds. This review focuses on recent developments in the structure optimization and biological evaluation of synthetic triterpenoid and steroid saponin derivatives. By summarizing the structure–activity relationship (SAR) results, we hope to provide the direction for future development of saponin-based bioactive compounds. Full article