Background and Purpose: Accumulating evidence indicates that mitochondrial dynamics play an important role in the progressive deterioration of dopaminergic neurons. Andrographolide has been found to exert neuroprotective effects in several models of neurological diseases. However, the mechanism of how andrographolide protects neurons in Parkinson's disease (PD) remains not fully understood.Experimental Approach: Behavioural experiments were performed to examine the effect of andrographolide in 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐PD mice. Mitochondrial mass and morphology were visualized using transmission electron microscopy (TEM). SH‐SY5Y cells and primary mouse neurons were exposed to rotenone to mimic PD in vitro. Western blotting, co‐immunoprecipitation and immunofluorescence were performed. The target protein of andrographolide was identified by biotin‐andrographolide pulldown assay as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), and surface plasmon resonance (SPR) assays.Key Results: Andrographolide administration improved behavioural deficits and attenuated loss of dopaminergic neurons in MPTP‐exposed mice and reduced cell death induced by rotenone in vitro. An increased mitochondrial mass, and decreased surface area were found in the striatum from MPTP‐PD mice, as well as in rotenone‐treated primary neurons and SH‐SY5Y cells, while andrographolide treatment preserved mitochondrial mass and morphology. Dynamin‐related protein 1 (DRP1) was identified as a target protein of andrographolide. Andrographolide bound to DRP1 and inhibited its GTPase activity, thereby preventing excessive mitochondria fission and neuronal damage in PD.Conclusions and Implications: Our findings suggest that andrographolide may protect neurons against rotenone‐ or MPTP‐induced damage in vitro and in vivo through inhibiting mitochondrial fission.

Asiatic acid (AA), a pentacyclic triterpene found in Centella asiatica, displays significant anti-proliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth both in vitro and in vivo and that the associated apoptosis is mediated through mitochondrial damage.