Protective effects of tetrahydropalmatine against ketamine-induced learning and memory injury via antioxidative, anti-inflammatory and anti-apoptotic mechanisms in mice

Zhang, Yonglai; Sha, Rui; Wang, Kaiguo; Li, Hao; Yan, Bingji; Zhou, Naibao

doi:10.3892/mmr.2018.8700

Cited by 13 publications

(11 citation statements)

References 37 publications

(43 reference statements)

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“…Inflammatory cytokines such as TNF- α and IL-6 play essential roles in the pathogenesis of ConA-induced liver injury [3, 26]. L-THP had anti-inflammatory effect by downregulating the expression of the inflammatory cytokines TNF- α and IL-6 [19, 27, 28]. However, function of L-THP pretreatment in ConA-induced AIH remains unknown.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects of Levo-Tetrahydropalmatine on ConA-Induced Liver Injury Are via TRAF6/JNK Signaling

Liu

et al. 2018

Mediators of Inflammation

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Aims Levo-tetrahydropalmatine (L-THP) is an active ingredient of Corydalis yanhusuo W. T. Wang, which has many bioactive properties. Herein, we investigated the protective effects of L-THP on concanavalin A- (ConA-) induced hepatitis in mice and explored its possible mechanisms of these effects. Main Methods Balb/c mice were intravenously injected with 25 mg/kg ConA to generate a model of acute autoimmune hepatitis, and L-THP (20 or 40 mg/kg) was administered orally once daily for 5 d before the ConA injection. The liver enzyme levels, proinflammatory cytokine levels, and other marker protein levels were determined 2, 8, and 24 h after ConA injection. Results L-THP could decrease serum liver enzymes and pathological damage by reducing the release of inflammatory factors like IL-6 and TNF-α. The results of Western Blot and PCR indicated that L-THP could ameliorate liver cell apoptosis and autophagy. L-THP could suppress T lymphocyte proliferation and the production of TNF-α and IL-6 induced by ConA in a dose-dependent manner in vitro. Additionally, the protective functions of L-THP depended on downregulating TRAF6/JNK signaling. Conclusion. The present study indicated that L-THP attenuated acute liver injury in ConA-induced autoimmune hepatitis by inhibiting apoptosis and autophagy via the TRAF6/JNK pathway.

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Section: Discussionmentioning

confidence: 99%

The Protective Effects of Levo-Tetrahydropalmatine on ConA-Induced Liver Injury Are via TRAF6/JNK Signaling

Liu

et al. 2018

Mediators of Inflammation

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“…Wang which has been widely used in traditional Chinese medicine for treating various pains and cardiovascular disease (Han et al, 2012; Kang et al, 2016). Previous studies have indicated that THP presented multiple pharmacological effects on cardio and neural tissues, such as cardioprotection, neuroprotection, anti-oxidant, anti-apoptosis, and anti-inflammation (Wu et al, 2010; Zhang et al, 2015, 2018). THP improved memory impairment, protected the blood brain barrier and cerebral ischemia-reperfusion injuries in experimental mice models (Mao et al, 2015; Cao et al, 2018; Sun et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Endothelial-Dependent and Independent Vascular Relaxation Effect of Tetrahydropalmatine on Rat Aorta

et al. 2019

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Tetrahydropalmatine (THP) is an active natural alkaloid isolated from Corydalis yanhusuo W.T. Wang which has been widely used for treating pain and cardiovascular disease in traditional Chinese medicine. Previous studies suggested THP have various pharmacological effects in neural and cardio tissue while the vascular reactivity of THP was not fully established. The present study found that THP relaxed rat aorta which contracted by phenylephrine (Phe), KCl, and U46619. The vascular relaxation effect of THP was partially attenuated by PI3K inhibitor wortmannin, Akt inhibitor IV, endothelial nitric oxide synthetase (eNOS) inhibitor L-NAME, guanylate cyclase inhibitors and the mechanical removal of endothelium. Also, the eNOS substrate L-arginine reversed the inhibition effect of L-NAME on THP-induced vascular relaxation. THP also induced intracellular NO production in human umbilical vein endothelial cells. However, Pre-incubation with β-adrenergic receptor blocker propranolol, angiotensin II receptor 1 (AT1) inhibitor losartan, angiotensin II receptor 2 (AT1) inhibitor PD123319 or angiotensin converting enzyme inhibitor enalapril enhanced the vascular relaxation effect of THP. THP did not affect the angiotensin II induced vascular contraction. Cyclooxygenase-2 (COX2) inhibitor indomethacin did not affect the vascular relaxation effect of THP. Furthermore, pre-treatment THP attenuated KCl and Phe induced rat aorta contraction in standard Krebs solution. In Ca 2+ free Krebs solution, THP inhibited the Ca 2+ induced vascular contraction under KCl or Phe stress and reduced KCl stressed Ca 2+ influx in rat vascular smooth muscle cells. THP also inhibited intracellular Ca 2+ release induced vascular contraction by blocking Ryr or IP3 receptors. In addition, the voltage-dependent K + channel (Kv) blocker 4-aminopyridine, ATP-sensitive K + channel (KATP) blocker glibenclamide and inward rectifying K + channel blocker BaCl 2 attenuated THP induced vascular relaxation regardless of the Ca 2+ -activated K + channel (KCa) blocker tetraethylammonium. Thus, we could conclude that THP relaxed rat aorta in an endothelium-dependent and independent manner. The underlying mechanism of THP relaxing rat aorta involved PI3K/Akt/eNOS/NO/cGMP signaling path-way, Ca 2+ channels and K + channels rather than COX2, β-adrenergic receptor and renin-angiotensin system (RAS). These findings indicated that THP might be a potent treatment of diseases with vascular dysfunction like hypertension.

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“…Yuanhuzhitong prescription comprised of Rhizoma Corydalis and A. dahurica could relieve various pains through activating or blocking the G-coupled protein receptors (GCPRs) such as 5-HT1A, OPRM1, ADRB2 receptors and block D 2 receptor which are mainly located in the central nervous system 25 . TDE, with bitter property, accounts for the main analgesic activity of Yuanhuzhitong prescription by blocking dopamine receptors in the central nervous system and depleting dopamine within the brain 26 , 27 . It was suggested that the TDE suppressed pain mainly within the brain region, so it is necessary for TDE to keep a certain concentration in the brain 24 , 25 .…”

Section: Discussionmentioning

confidence: 99%

Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription

Wang

Hong

et al. 2020

Acta Pharmaceutica Sinica B

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Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising Corydalis yanhusuo (CYH) and Angelica dahurica (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3. What's more, AD extract also exerted strongly inhibition to human transporters OATP1B1 and OATP1B3. It was also detected that IPT, ISP, and AD extract significantly downregulated the expression of Oatp1a1 , Oatp1a4 , and Oatp1b2 of liver in mice. The in vivo results show that the concentration of TDE in liver and kidney significantly decreased, while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT, ISP, and AD extract. These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney. That is to say, TDE with bitter taste could “flood up” into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD. This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3, OATP1B1, and OATP1B3, but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD. This study may offer a valuable clue to illustrate the mechanism of compatibility theory.

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Protective effects of tetrahydropalmatine against ketamine-induced learning and memory injury via antioxidative, anti-inflammatory and anti-apoptotic mechanisms in mice

Cited by 13 publications

References 37 publications

The Protective Effects of Levo-Tetrahydropalmatine on ConA-Induced Liver Injury Are via TRAF6/JNK Signaling

The Protective Effects of Levo-Tetrahydropalmatine on ConA-Induced Liver Injury Are via TRAF6/JNK Signaling

Endothelial-Dependent and Independent Vascular Relaxation Effect of Tetrahydropalmatine on Rat Aorta

Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription

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