Tcm for hemostatic derangement: A scoping review of herb-based molecules active against COVID-19 coagulopathy

ABSTRACT

Background: COVID-19 is a multiple-system inflammatory disease with a wide range of symptoms from none at all or resembling a mild cold, to severe fatigue, pain, and shortness of breath. Severe cases are often fatal, and usually involve multiorgan failure, myocardial infarction, venous thromboembolisms, cerebral vascular accident, and other ischemic events. Systemic hypercoagulability and thrombosis are caused by catastrophic dysregulation of the immune, inflammatory, and coagulation responses to SARS-COVID-2. The pressures of variable mask wearing agreement, slow vaccine distributions, and new, more transmissible variants obstructing herd immunity motivate the search for therapeutic solutions within traditional Chinese medicine. Methods: We conducted a PubMed systematic review for citations assessing effects of a pre-determined set of candidate herbs on a pre-determined set of molecular markers involved in COVID-19 associated coagulopathy. Candidate blood moving herbs were those included in 28 published traditional medicine COVID-19 treatment guidelines. Pathomechanisms and molecular markers were cross-referenced against herbal actives, and by functional strategies. Results: Of particular interest are those herbs acting on the receptor protein (NLRP3) inflammasome pathway, neutrophil extracellular trap (NET) formation and release of active coagulation factors, and endothelial dysfunction. Many Chinese herbs are active against COVID-19 coagulopathy cinnamon twig (Gui Zhi), schizonepata herb ( Jing Jie) and hawthorn fruit (Shan Zha) downregulate the IL-18 inflammasome;ginseng (Ren Shen), peony root (Paeonia alba) and Japanese knotweed (Polygonum cuspidatum) down-regulate the NLRP-3 inflammasome formation. Both the IL-18 and NLRP-3 inflammasomes are upregulated by and play a role in COVID-19 coagulopathy. Attenuating these inflammasomes inhibits the systemic inflammatory response syndrome, by down-regulating IL-1β, IL-6 and TNF-α. Interpretation: Coagulopathy is a key driver of the systemic damage caused by COVID-19 infection. The potential relevance of Chinese herbal medicines playing a significant role in COVID-19 may rest on their ability to attenuate the inflammasomes driving the systemic inflammatory response syndrome.