International Journal of Clinical Case Reports 2024, Vol.14, No.5, 262-275 http://medscipublisher.com/index.php/ijccr 271 commonly used in China for treating osteoporosis but also has implications for hypertension due to its multi-component, multi-target, and multi-pathway interaction mechanisms (Feng et al., 2022). Figure 3 Correlation of intestinal microbiota and metabonomics (Adopted from Qi et al., 2020) Image caption: The vertical direction represents the differential bacteria at the level of 16S OTUs (species, genus), and the horizontal direction represents the names of differential metabolite. The value range of the correlation coefficient is (-1, +1). The intestinal microbiota and fecal metabolites show∣rho|>=0.7 and p < 0.05, which is considered to demonstrate a high correlation and a significant effect. The red oval indicates a positive correlation, and the blue oval indicates a negative correlation between the intestinal microbiota and fecal metabolites (Adopted from Qi et al., 2020) 8.2 Synergistic effects observed in preclinical studies Preclinical studies have demonstrated that the combination of Eucommia ulmoides with other herbs can lead to enhanced antihypertensive effects. For instance, the ET combination was found to significantly decrease blood pressure in SHRs, which was associated with changes in the intestinal microbiota and fecal metabolism. The treatment increased the abundance of beneficial microbes like Eubacterium, which correlated with decreased levels of harmful metabolites such as α-tocopherol, chenodeoxycholic acid, and deoxycholic acid (Qi et al., 2020). Additionally, the Eucommia ulmoides bark extract has been shown to reduce blood pressure and inflammation by regulating the gut microbiota and enriching the Parabacteroides strain in high-salt diet and N(omega)-nitro-L-arginine methyl ester (L-NAME) induced mice. This suggests that the gut microbiota plays a crucial role in the antihypertensive effects of Eucommia ulmoides (Yan et al., 2022). Moreover, the Eucommia ulmoides–Tribulus terrestris drug pair has been studied for its potential to regulate ferroptosis by mediating the neurovascular-related ligand-receptor interaction pathway. This drug pair was found to interact with proteins related to the ferroptosis pathway, which could potentially affect the onset and progression of hypertension-associated neurovascular lesions and ischemic stroke (Zhang et al., 2022). 8.3 Implications for clinical practice The observed synergistic effects of Eucommia ulmoides when combined with other herbs have significant implications for clinical practice. The combination therapies could offer a more effective approach to managing hypertension, especially in patients who do not respond well to conventional treatments. The ET combination, for example, could be particularly beneficial for elderly patients with hypertension, as it not only lowers blood pressure but also improves gut health and reduces harmful metabolites (Qi et al., 2020). Furthermore, the ability of Eucommia ulmoides to modulate the gut microbiota and reduce inflammation suggests that it could be used as a complementary therapy alongside probiotics and prebiotics to enhance its antihypertensive effects (Yan et al., 2022). The Eucommia ulmoides–Tribulus terrestris drug pair's
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