Combination of Danshen and ligustrazine has dual anti-inflammatory effect on macrophages and endothelial cells

Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The multi-component and multi-targeted approach of natural products have the potential to manage CVDs. This review aims to provide a comprehensive insight into the synergistic mechanism of natural product combinations in protecting the endothelium against various cardiovascular risk factors. Databases (PubMed, MEDLINE and EMBASE) and Google Scholar were searched, and studies in English published between January 2000 and February 2022 were collated. Clinical and pre-clinical studies of natural product combinations with or without pharmaceutical medicines, compared with monotherapy and/or proposing the underlying mechanism in protecting endothelial function, were included. Four clinical studies demonstrated that natural product combinations or natural product-pharmaceutical combinations improved endothelial function. This was associated with multi-targeted effects or improved absorption of the active substances in the body. Seventeen preclinical studies showed that natural product combinations produced synergistic (demonstrated by combination index or Bliss independence model) or enhanced effects in protecting the endothelium against hyperlipidemia, hypertension, diabetes mellitus, platelet activation, oxidative stress and hyperhomocysteinemia. The molecular targets included reactive oxygen species, Nrf2-HO-1, p38MAPK, P13K/Akt and NF-κB. Thus, the current available evidence of natural product combinations in targeting endothelial dysfunction is predominantly from preclinical studies. These have demonstrated synergistic/enhanced pharmacological activities and proposed associated mechanisms. However, evidence from larger, well-designed clinical trials remains weak. More cohesion is required between preclinical and clinical data to support natural product combinations in preventing or slowing the progression of CVDs.

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“…Bioinformatic analysis revealed that IL-6 gene and C-X-C modify chemokine ligand 10 (CXCL10) appeared to be involved in the mechanism. 62 …”

Section: Resultsmentioning

confidence: 99%

Synergistic Effects of Natural Product Combinations in Protecting the Endothelium Against Cardiovascular Risk Factors

Yousaf

Razmovski-Naumovski

Zubair

et al. 2022

J Evid Based Complementary Altern Med

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“…Similarly, Chuanxiong promotes blood vessel dilation and eliminates blood stasis. According to previous research, [ 44 ] Danshen has an obvious anti-inflammatory effect on bone marrow macrophages. However, it has minimal effect on human umbilical vein endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Salviae miltiorrhizae and ligustrazine hydrochloride injection combined with mecobalamin for treating diabetic peripheral neuropathy

et al. 2021

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Objective: Currently, it is unclear whether the salviae miltiorrhizae (Danshen Salvia) and ligustrazine hydrochloride (Chuanxiong Chuanxiong) (SMLH) injection combined with mecobalamin can improve diabetic peripheral neuropathy (DPN). We conducted a systematic analysis to evaluate the clinical effects of SMLH injection combined with mecobalamin for treating DPN. Methods: Seven databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wang Fang), Chinese Biomedical Literature Database (CBM), and VIP Database for Chinese Technical Periodicals (VIP) were searched for systematic literature retrieval. Each database was searched up to 2020 to identify randomized controlled trials on DPN treated with SMLH injection combined with mecobalamin. We used the RevMan 5.3 and Stata 14.0 software to assess the risk of bias in the included trials. Results: A total of 15 publications, including 1349 samples, were reviewed. The total effective rate of SMLH injection combined with mecobalamin was 31% higher than that of mecobalamin alone (95% confidence interval [CI] = 1.23–1.38; P < .00001). The experimental group showed a significant increase in the motor conduction velocity (MCV) of the peroneal nerve (weighted mean difference [WMD] = 4.81, 95% CI 3.53–6.09; P < .00001). In addition, SMLH injection combined with mecobalamin showed a statistical significant effect on the sensory conduction velocity (SCV) of the peroneal nerve (WMD = 5.03, 95% CI = 4.16–5.90; P < .00001), and MCV of the median nerve (WMD = 5.38, 95% CI = 4.05–6.72; P < .00001). The WMD for the change in SCV in the median nerve was 4.89 m/s (95% CI = 3.88–5.89; P < .00001). The P-values of the Egger and Begg tests were 0.967 and 0.961, respectively, indicating no publication bias. Subgroup and sensitivity analyses indicated that the results for MCV and SCV of the peroneal nerve and the median nerve were stable. Conclusion: SMLH injection combined with mecobalamin can improve DPN, compared with mecobalamin alone.

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“…Several studies have suggested that the pathogenesis of COVID-19 involves an inability to resolve the inflammatory response along with the activation of immune cells and inflammatory cytokines ( 18 , 34 ). In COVID-19 patients, an unregulated inflammatory response to the infection can result in the dysregulation of T cells with associated lymphopenia, high levels of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and high levels of inflammatory chemokines, including C-C motif chemokine ligand (CCL-2) ( 35 ). In a study by Staats et al, 49-year-old man with excessive fatigue, mental cloudiness and body aches, and mental cloudiness had ceased after 5 days non-invasive VNS therapy ( 19 ).…”

Section: The Important Link Between Proinflammatory Cytokines and Covid-19 Pandemic-related Multiorgan Damagementioning

confidence: 99%

Use of Transcutaneous Auricular Vagus Nerve Stimulation as an Adjuvant Therapy for the Depressive Symptoms of COVID-19: A Literature Review

et al. 2021

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The coronavirus disease 2019 (COVID-19) comprises more than just severe acute respiratory syndrome. It also interacts with the cardiovascular, nervous, renal, and immune systems at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Transcutaneous auricular vagus nerve stimulation (taVNS), which is derived from auricular acupuncture, has become a popular therapy that is increasingly accessible to the general public in modern China. Here, we begin by outlining the historical background of taVNS, and then describe important links between dysfunction in proinflammatory cytokine release and related multiorgan damage in COVID-19. Furthermore, we emphasize the important relationships between proinflammatory cytokines and depressive symptoms. Finally, we discuss how taVNS improves immune function via the cholinergic anti-inflammatory pathway and modulates brain circuits via the hypothalamic–pituitary–adrenal axis, making taVNS an important treatment for depressive symptoms on post-COVID-19 sequelae. Our review suggests that the link between anti-inflammatory processes and brain circuits could be a potential target for treating COVID-19-related multiorgan damage, as well as depressive symptoms using taVNS.

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Combination of Danshen and ligustrazine has dual anti-inflammatory effect on macrophages and endothelial cells

Cited by 25 publications

References 26 publications

Synergistic Effects of Natural Product Combinations in Protecting the Endothelium Against Cardiovascular Risk Factors

Synergistic Effects of Natural Product Combinations in Protecting the Endothelium Against Cardiovascular Risk Factors

Salviae miltiorrhizae and ligustrazine hydrochloride injection combined with mecobalamin for treating diabetic peripheral neuropathy

Use of Transcutaneous Auricular Vagus Nerve Stimulation as an Adjuvant Therapy for the Depressive Symptoms of COVID-19: A Literature Review

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