The Potential of Tetrandrine as a Protective Agent for Ischemic Stroke

Abstract

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.

Renalase Attenuates Mouse Fatty Liver Ischemia/Reperfusion Injury through Mitigating Oxidative Stress and Mitochondrial Damage via Activating SIRT1

“…Suppressing ROS burst in oxidative stress is an efficient way to alleviate liver IR injury. Antioxidant strategies, including ischemia preconditioning (IPC) [38], and antioxidant pharmacological therapies, including N-acetylcysteine [39], α-tocopherol [40], β-carotene [41], vitamin C [42], trans-resveratrol [43], tetrandrine [44], and extracts from green tea [45], grape seeds [46], and other plants, confer protection from liver IR injury by attenuating oxidative stress and maintaining the cellular redox balance. Catecholamines, including dopamine, are subjected to autoxidation and produce ROS [47], which is implicated in IR injury [48,49].…”

Tetrandrine is a potent cell autophagy agonist via activated intracellular reactive oxygen species

“…Tetrandrine is one member of the bisbenzylisoquinoline alkaloids isolated from the root of a traditional Chinese medicinal herb, Stephaniae tetrandrae , which has been broadly applied in clinical treatment for thousands of years in China [ 14 ]. In recent decades, it has been used to treat patients with rheumatoid arthritis [ 15 ], hypertension [ 16 ], sepsis [ 17 ], inflammation [ 18 , 19 ], occlusive cardiovascular disorders [ 20 ] and silicosis [ 21 ] in modern medicine [ 22 – 24 ]. Due to its action on intracellular multiple signaling molecules and relatively low toxicity to humans even when administered at high doses, tetrandrine has been attracted considerable attention as an antitumor therapeutic [ 25 – 28 ].…”

Tetrandrine alleviates symptoms of rheumatoid arthritis in rats by regulating the expression of cyclooxygenase‑2 and inflammatory factors

“…Tet comprises ~1% of the root of Stephaniae tetrandrae Radix (23), and has been documented to have numerous pharmacological effects (24), including anti-myocardial ischemia activities, inhibitory effects on platelet aggregation (25) and spasmolytic (26), anti-tumor (27), analgesic, anti-inflammatory (28), anti-ulcer and hepatoprotective effects (29,30). Tet has also been implicated in the regulation of immunity (31), hypoxia tolerance (14) and suppression of rheumatalgia, arthralgia and neuralgia (32,33).…”

“…Tet also increases cardiac output and exerts muscle relaxant, antipyretic, analgesic and anti-inflammatory effects, and may inhibit cell proliferation and induce apoptosis (12,13). In addition, Tet tablets may be used for the treatment of simple silicosis, anthracosilicosis, mild hypertension, rheumatalgia, arthralgia and neuralgia (14)(15)(16). However, it is not clear whether Tet is effective in the treatment of patients with RA and the mechanism of action of Tet on RA remains unknown.…”