Efficacy and Safety of Panax notoginseng Saponin Therapy for Acute Intracerebral Hemorrhage, Meta-Analysis, and Mini Review of Potential Mechanisms of Action

Abstract

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.

Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

“…Panax notoginseng saponins (PNS), the main effective ingredients of P. notoginseng, are clinically used in the prevention and treatment of cerebrovascular diseases in China, such as ischemic stroke (Zhang, Wu, & Zhang, 2015). So far, most scientists focus their research attention on the effects of PNS concerning blood dynamics invigoration, anti-thromboembolism, anti-coagulation, anti-hyperglycemia, antihyperlipidemia, anti-edema, and neroprotection (Xu et al, 2015) but ignoring the effect on BBB (brain microvasculature). What is more, previous report demonstrated that early BBB disruption might be a cause rather than a consequence of brain neuron injury in several cerebral disease (Shi et al, 2016).…”

Administration of Yunnan Baiyao improved clinical prognosis of emergency craniotomy in patients with moderate-to-severe TBI: a randomized controlled trial

“…Intracranial bleeding, edema and coagulopathy are major predictors of mortality and morbidity of TBI that still lacks of effective therapy [9,53,54]. YB and its major active ingredient Notoginseng saponins (PNS) have dual anti-hemorrhage and anti-hemostasis properties [19,55]. YB showed signi cantly better antibleeding e cacy (92•30%) than pantoloc (71•20%) in severe TBI-induced stress gastrointestinal bleeding and ulcer [21,22] and is more effective in controlling gastrointestinal tract in ammation in colitis model of in ammatory bowel disease (IBD), by suppressing pro-in ammatory cytokine expression (including TNFa, IL-12p40, and IL-17) and T-and B-lymphocytes, and but promoting intestinal epithelial wound-healing/repairing [56].…”

Evidence‐based practice guideline on integrative medicine for stroke 2019

“…As always, patient safety should be a priority. There were systematic reviews supporting the effectiveness and safety of Notoginseng total saponins injections 67 and Naoxueshu oral solution 68 as add‐on treatment in patients receiving routine treatment for hypertensive intracranial hemorrhage. Injections containing Notoginseng total saponins include Xueshuantong and Xuesaitong; however, Xuesaitong injection is not recommended because of its instructions for use state that it is contraindicated in acute hemorrhagic stroke.…”