Paper Title
Combination of Artesunatand Brotowali (Tinosporacrispa) Extract Decreases the Heat Shock Protein(HSP)-70 Expressions in Liver and Spleen Tissue of Mice that Infected with Plasmodium Berghei.

Abstract
During malaria infection there is an increase of Heat Shock Protein 70 (HSP70)caused by excess free radicals production that related to oxidative stress. Brotowali(Tinosporacrispa(L) Miers)contains variety of active ingredients, such as berberine, palmatinandtinokrisposid that can serve as anti-malarial andphenolic compounds that can act asanti-inflammatory activity, as welll as bergenin, N-cis-feruloytyramine, N-trans feruloytyramine known to have antioxidant effects.Administrationof a combination of brotowali(Tinosporacrispa(L) Miers) extracts and artesunate the first malaria drug line, expeccted to control the excessive production of free radicals as a result of malaria infection. The goal of this study was to prove the effect of methanol stem brotowali (Tinosporacrispa(L) Miers) extract a lone and in combination with artesunate therapy on the expression of HSP70 in liver and spleen tissue of mice infected by Plasmodium berghei, a human malaria model. This research was an experimental study using post test only controlgroup design. Mice were grouped randomly into 6 groups, namely the negative control, positive control group, the group treated with the extract brotowaliwith a dose of 70 mg/day, the group treated with combination of artesunate and extract brotowaliin a dose of 50, 60, and 70 mg/day respectively. The treatment was done for 14 days. Parameters measured were HSP70 expression of liver and spleen tissue observed byimunohistochemistrystaining. The results showed that methanol brotowali stem (Tinosporacrispa(L.) Miers) extract had a strong potential to decrease HSP70 expression in liver andspleen of mice infected by Plasmodium berghei(p<0,05). The higher doses of methanol brotowali (Tinosporacrispa (L) Miers) stem extract, the lower the expression of HSP70 in liver and spleen tissue of mice infected by Plasmodium berghei (p= 0.000 and r= -0,83; p= 0.000 and r=-0,90) It was concluded that the methanol extract brotowali (Tinosporacrispa (L) Miers) has a potential to decrease the HSP70 expression in the liver and spleen tissue of mice infected byPlasmodium berghei. Keywords - Malaria, Brotowali stem (Tinospora crispa (L) Miers), HSP70, Plasmodium berghei, Artesunat, liver, Spleen