Effets anti-inflammatoires des extraits et fractions polysaccharidiques des écorces de Khaya grandifoliola (Welw) C.D.C et des feuilles de Cryptolepis sanguinolenta (Lindl.) Schlechter

Abstract

Khaya grandifoliola (Meliaceae) and Cryptolepis sanguinolenta (Apocynaceae) are two plants of the Cameroonian pharmacopoeia used in the treatment of several health problem such as fever, headaches, Malaria and liver disorders. Several studies conducted on the crude extracts of these plants led to the identification of bioactive secondary metabolites (grandifotan A, cryptolepin ...). Although extractable by traditional preparations, very few studies have investigated the role of polysaccharides in the therapeutic efficacy of these plants. In order to pursue the valorization of K. grandifoliola and C. sanguinolenta, anti-inflammatory activities of polysaccharide extracts and fractions of bark and leaves respectively were evaluated in vitro using PBMCs mononuclear cells, RAW 264.7 macrophages and U87 cancerous glial cells. Total polysaccharide extract of K. grandifoliola (PoSKG) mainly contains Glucose (30.53 %), Galactose (28.89 %) and Arabinose (17.51 %). While PoSCS is rich in Glucose (60.51 %) and contains low levels of Arabinose and Galactose. The pectins of both plants are mainly rhamnogalacturonan type I and hemicelluloses are arabinoxylans or xyloglucans. PoSKG and PoSCS highly complexed with proteins and phenolic compounds, have demonstrated the best ABTS antiradical activities and inhibitory activities of IL-6, IL1-β and TNF-α pro inflammatory cytokines production by PBMCs (p <0.001). They were subsequently délipidated, depigmented, fractionated in low (FKG and FCS) and high (HKG and HCS) molecular weight, and deproteinized. Only K. grandifoliola polysaccharide fractions (FKG and HKG) inhibit from 10 µg/mL intracellular production of Reactive Oxygen Species (ROS) induced by LPS in U87 cells. Furthermore, FKG 100 µg/mL showed a higher activity against Nitric Oxide (NO) production induced by LPS (63.32%) comparable to 1 µM aspirin activity (64.85 %) (p<0.001). Otherwise, FKG (10 µg/mL) and HKG (100 µg/mL) attenuated LPS induced cell death in U87 while inhibiting at the transcriptional level the expression of TNF α, IL-6, IL-1β and NF-κB (p <0.001). In vivo, oral administration of FKG and HKG to BALB/c mice at 100 mg/kg attenuate pain induced by chemical and thermal stimuli. In addition, FKG and HKG fractions demonstrated inhibitory activity of transcription of brain pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) genes dependent on inhibition of the NF-κB signaling pathway, induced by LPS.