Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacognocy

Damsissa (Ambrosia maritima L.) was traditionally used as anti-inflammatory and diuretic, yet with no adequate scientific evidence. Damsin and neoambrosin are two major anticancer phytopharmaceuticals of Damsissa. Our target was to elucidate the mechanism of action of the anti-arthritic potential of damsin (DMS) and neoambrosin (NMS) and to unfold their molecular signaling in complete Freund{u2019}s adjuvant (CFA)-induced arthritis model. DMS and NMS were isolated utilizing different chromatographic techniques. Their chemical identity and purity were assessed by 1H-, 13C-NMR, HPLC. The pharmacological study verified that, treatments ameliorated the increase of paw volume, knee joint diameter and nociception tests. Also, DSM and NMS suppressed phosphorylation of transcription factors Akt, STAT-3, ERK1/2 which was further mirrored by inactivation and suppression of inflammatory and chemotactic factors. DMS and NMS-induced suppression of NF-kÝ subdues clinical features of RA most probably through repression of Akt/ERK1/2/STAT3 pathway. Therefore, DMS and NMS can serve as safe and effective treatment for rheumatoid arthritis, one of the most disabling chronic, inflammatory and painful autoimmune disease.After verifying the pharmacological efficacy of DMS and NMS we aimed to develop an ultrasonic-assisted extraction (UAE) model as a green extraction method for their extraction on the lab scale. Box-Behnken model was applied to investigate the effects of ethanol strength (X1: 40-100%), drug solvent ratio (DSR, X2: 1:20-1:60), and time (X3: 30-90 min) on the yield of damsin and neoambrosin in Damsissa extract. Surprisingly, only ethanol strength was the significant factor in damsin yield with an optimum value of 55%. Time and DSR played no significant roles in damsin content. No statistically significant model could be deduced for neoambrosin

Issued also as CD