Application of promoting blood circulation and resolving blood stasis in intracerebral hemorrhage: a traditional method gradually being reconsidered

Abstract

Intracerebral hemorrhage (ICH) is a significant and growing threat to human health, with increasing incidence. Promoting blood circulation and removing blood stasis therapy (PBCRBS), a Traditional Chinese Medicine therapy, can be an adjuvant therapy to benefit patients with ICH by improving clinical efficacy. However, in theory, using PBCRBS to treat ICH carries the risk of hematoma enlargement and rebleeding, which has led to controversy over its application in ICH treatment. To demonstrate the effectiveness and safety of PBCRBS in treating ICH, this review first analyzes the pathological and physiological basis of ICH and secondly, the cascade of response after ICH and the involvement of cytokines and signaling pathways in this process. Finally, experimental and clinical studies on the treatment of ICH with PBCRBS over the past decade were retrieved from the PubMed and China National Knowledge Infrastructure databases, and the content of these studies was used to summarize commonly used herbs with PBCRBS effects and their mechanisms of action. Through analysis, hypertension has been identified as the most common cause of ICH. Heme, interleukin, reactive oxygen species, coagulation promoting particles and other induced mass effects, inflammation, oxidative stress, and coagulation cascade reactions lead to brain damage following ICH. This review includes 56 experimental studies and 83 clinical studies summarizing 28 commonly used herbs, demonstrating the positive impact of PBCRBS as an adjuvant therapy for ICH. In summary, PBCRBS appears effective and safe for treating ICH.

Keywords: cerebral hemorrhage; etiology; medicine, Chinese traditional; pathology; physiopathology; promoting blood circulation and removing blood stasis; review.

Figure 1. The pathological and physiological bases of ICH

ICH: intracerebral hemorrhage.

Figure 2. The role of cytokines and signaling pathways in brain injury and repair after ICH

ICH: intracerebral hemorrhage; TJ protein: tight junction; AQP-4: aquaporin-4; TIMP-1: tissue inhibitors of metalloproteinases-1; Fe²⁺: ferrous iron; Fe³⁺: ferric iron; BV: biliverdin; CO: carbon monoxide; Fe: free iron; Ca²⁺: calcium; MMP-9: matrix metalloproteinase-9; HO: heme oxygenase; RhoA/ROCK: RhoA/Rho-associated kinase; Hb: hemoglobin; RBC: red blood cell; M1: pro-inflammatory microglia; M2: repair microglia; IL: interleukin; TNF-α: tumor necrosis factor-α; ICAM-1: intercellular cell adhesion molecule-1; ROS: reactive oxygen species; SOD: superoxide dismutase; Prx: peroxidase; GSH: glutathione; GSH-Px: glutathione peroxidase; VitE: vitamin E; Lip: lipids; Pr: protein; NA: nucleic acids; MDA: malondialdehyde; 3-NT: 3-nitrotyrosine; 8-OHDG: 8-hydroxy deoxyguanosine; Nrf2: nuclear factor erythroid 2-related factor 2; ARE: antioxidant response elements; CAT: catalyst; RNS: reactive nitrogen species; PLT: platelet; cFN: cell fibronectin; PAR-1: protease-activated receptor-1; PTK: protein tyrosine kinase; JAK-STAT: janus kinase/signal transducer and activator of transcription; APE: apurinic/apyrimidinic endonuclease; ATF: activating transcription factor; GRP: glucose regulatory protein; PERK: protein kinase R-like ER kinase; IRE1: inositol requiring enzyme 1; ERS: endoplasmic reticulum stress; UPR: unfolded protein response; Cytc: cytochrome c; GSK-3β: glycogen synthase kinase-3β; PI3K-Akt: PI3 kinase-Akt; Bcl-2: B-cell lymphoma-2.

Figure 3. The process of thrombosis and the therapeutic effects of PBCRBS

ICH: intracerebral hemorrhage; PBCRBS: promoting blood circulation and removing blood stasis therapy.

Figure 4. Overview of the critical mechanisms in the treatment of ICH with PBCRB

ICH: intracerebral hemorrhage; PBCRBS: promoting blood circulation and removing blood stasis therapy.