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Intracranial/intracerebral hemorrhage (ICH) is a leading cause of death and disability in people with traumatic brain injury (TBI) and stroke. No proven drug is available for ICH. Panax notoginseng (total saponin extraction, PNS) is one of the most valuable herb medicines for stroke and cerebralvascular disorders in China. We searched for randomized controlled clinical trials (RCTs) involving PNS injection to treat cerebral hemorrhage for meta-analysis from various databases including the Chinese Stroke Trials Register, the trials register of the Cochrane Complementary Medicine Field, the Cochrane Central Register of Controlled Trials, MEDLINE, Chinese BioMedical disk, and China Doctorate/Master Dissertations Databases. The quality of the eligible trials was assessed by Jadad’s scale. Twenty (20) of the 24 identified randomized controlled trials matched the inclusive criteria including 984 ICH patients with PNS injection and 907 ICH patients with current treatment (CT). Compared to the CT groups, PNS-treated patients showed better outcomes in the effectiveness rate (ER), neurological deficit score, intracranial hematoma volume, intracerebral edema volume, Barthel index, the number of patients died, and incidence of adverse events. Conclusion: PNS injection is superior to CT for acute ICH. A review of the literature shows that PNS may exert multiple protective mechanisms against ICH-induced brain damage including hemostasis, anti-coagulation, anti-thromboembolism, cerebral vasodilation, invigorated blood dynamics, anti-inflammation, antioxidation, and anti-hyperglycemic effects. Since vitamin C and other brain cell activators (BCA) that are not considered common practice were also used as parts of the CT in several trials, potential PNS and BCA interactions could exist that may have made the effect of PNS therapy less or more impressive than by PNS therapy alone. Future PNS trials with and without the inclusion of such controversial BCAs as part of the CT could clarify the situation. As PNS has a long clinical track record in Asia, it could potentially become a therapy option to treat ICH in the US and Europe. Further clinical trials with better experimental design could determine the long-term effects of PNS treatment for TBI and stroke.

Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD+ and ATP depletion, and AIF nucleus translocation. Now, it is reported that parthanatos widely exists in different diseases (tumors, retinal diseases, neurological diseases, diabetes, renal diseases, cardiovascular diseases, ischemia-reperfusion injury...). Excessive or defective parthanatos contributes to pathological cell damage; therefore, parthanatos is critical in the therapy and prevention of many diseases. In this work, the hallmarks and molecular mechanisms of parthanatos and its related disorders are summarized. The questions raised by the recent findings are also presented. Further understanding of parthanatos will provide a new treatment option for associated conditions.