Bioassay‐guided isolation of anti‐inflammatory diterpenoids with highly oxygenated substituents from kidney tea ( Clerodendranthus spicatus )

Abstract

The whole plant of Clerodendranthus spicatus (Thunb.) is one of popular functional food in south of China, named as "kidney tea" and used to ameliorate renal inflammation. In order to verify this potential function and explore the accurate compounds responsible for inflammation, the ethanol extract, fractions, and subfractions of this plant were prepared to evaluate anti-inflammation effect on xylene-induced acute inflammatory mice model, and the results indicated that two subfractions from EtOAc fraction show potential activities. Subsequent bioassay-guided isolation of the bioactive subfractions led to isolation of 25 compounds. Among them, compounds 2, 4, 5, 9-11, 13, 16, 17, and 20-22 inhibited the productions of pro-inflammation factors TNF-α, IL-1β, and IL-8 in lipopolysaccharide (LPS)-induced renal epithelia (HK-2) cells, respectively. Further anti-inflammation evaluation in vivo indicated that the major bioactive compounds 1, 2, 5-7, 17, 21, and 22 from C. spicatus were even better than aspirin. Practical applications C. spicatus as a healthy tea has been available in the Chinese market and as a medicine for various disorders such as nephritis, rheumatism, inflammation, gout, and diabetes. Previous pharmacological investigation of the plant revealed the potential antiinflammatory activities, but the material basis of anti-inflammatory activity remains to be elucidated. In our study, the anti-inflammatory fractions and compounds were obtained by the bioassay-guide isolation and the results showed that the highly oxygenated diterpenoids were major anti-inflammatory compounds, in which 1, 2, 5-7, 17, 21, and 22 were even better than aspirin. This information supported kidney tea as a functional food for treatment of renal inflammation reasonably and may add a new dimension to biological activity of this plant in the field of agriculture as a functional food were cultivated.

A Systematic Review of Orthosiphon stamineus Benth. in the Treatment of Diabetes and Its Complications

“…Some compounds isolated from EtOAc fractions, orthosiphol M, orthosiphonone A, orthosiphol B, neoorthosiphol A, orthosiphol D, fragransin B 1 , sinensetin and 5, 6, 7, 4 -tetramethoxyflavone, also showed marked repression in the observed auricle swelling at the dose of 50 mg/kg. Besides, some of these compounds inhibited pro-inflammatory cytokines production in lipopolysaccharide (LPS)-induced HK-2 cells, such as the levels of TNF-α, IL-1β, and IL-8 [56]. The isolated compounds (clerodens A-D) were studied for anti-inflammatory activities on LPS-induced NO production in RAW264.7 macrophages.…”

The Chemistry and the Anti-Inflammatory Activity of Polymethoxyflavonoids from Citrus Genus

“…Compounds 5 and 33 were found to inhibit the expression of the enzymes involved in the inflammatory response of LPS-activated RAW267.4 cells as they significantly reduced the mRNA expression of IL-1β, TNF-α, IL-6, COX-2, and iNOS [114]; iNOS and COX-2 were deeply downregulated in the same cell type by compound 17 at 10 µM [115]. Further, IL-1β and TNF-α were also effectively reduced in LPS-activated renal epithelia HK-2 cells by compounds 3, 17, 25, and 45 [116]. The antiinflammatory activity of 17 was also proven for another biological model, LPS-activated THP-1 monocytic leukemia cells, where this compound inhibited IL-6 release [117].…”

“…Compounds 17 and 45 confirmed the anti-inflammatory potential disclosed in vitro (see above) in the in vivo xylene-induced ear edema test. They were able to remarkably reduce the auricle swelling at a dose of 50 mg/Kg [116].…”