In vitro study using RT-PCR showed that nanoherbal reliability reduced HIF1α expressions at 16 h. This herbal increased gene activity at 30 min, 1 h to 3 hours3h compared to the control group, and HIF1α activity remained stable in the control group. Increased HIF1α activity at 30 minutes, 1h to 3 h treatment is associated with hypoxic signaling for drug therapy and toxicity, which may affect the HIF-mediated balance between adaptation and cell death. Cells under hypoxic stress can induce responses that include an increase in the rate of glycolysis and angiogenesis or experience cell death resulting in apoptosis or necrosis (37). Changes of HIF1α expression that increase for 30 min, then decrease at the last time of treatment (overnight), allowing cell death or adaptation. Adaptation in mammalian cells, particularly placental cells under low oxygen conditions is largely mediated by the induction of transcription of gene expression. The stability and activity of HIF-1α are regulated by post-translational modification, chaperone functions, and alternative splicing (38). Hypoxia is known to induce HIF-1α transiently, largely as a result of protein stabilization. The increase of HIF-1α expression on andaliman administration in the first time treatment also is thought to be due to the compounds in these herbs. Andaliman also contains many steroids or sitosterols as protection from insect attack (insecticides) in plants and these compounds have a negative effect on liver cells .