Prevention of gallstones by Lidan Granule: Insight into underlying mechanisms using a guinea pig model

Wu, Xiao; Liang, Xiaoqiang; Du, Yanqiu; Zhang, Yan; Yang, Meng; Gong, Wei; Liu, Baojun; Dong, Jingcheng; Zhang, Ningxia; Zhang, Hongying

doi:10.3892/br.2016.672

Cited by 8 publications

(7 citation statements)

References 25 publications

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“…In the present study, hypercholesterolemia was successfully induced, and elevated levels of T-CHOL in the bile from guinea pigs were observed when fed a LD for 2 or 8 weeks. Several studies have shown that a LD facilitates the formation of cholesterol gallstones in guinea pigs ( 21 , 22 ). Hence, in the present study, LD-fed guinea pigs were used to investigate the possible mechanisms underlying gallbladder hypomotility in the development of cholesterol cholelithiasis.…”

Section: Discussionmentioning

confidence: 99%

Changes in the interstitial cells of Cajal in the gallbladder of guinea pigs fed a lithogenic diet

Huang

Ding

2021

Exp Ther Med

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Cholesterol cholelithiasis is a common disease and gallbladder hypomotility may underlie its pathogenesis. Interstitial cells of Cajal (ICCs) in the gallbladder serve vital roles in regulating gallbladder motility. The aim of the present study was to investigate changes in gallbladder ICCs during the development of cholesterol cholelithiasis. A total of 40 male guinea pigs were randomly assigned to four groups and fed a standard diet (SD) or lithogenic diet (LD) for 2 or 8 weeks. The LD significantly increased the total cholesterol levels in the serum and bile, as well as the serum levels of high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol after 2 and 8 weeks. The LD also significantly increased and decreased the number of gallbladder ICCs at 2 and 8 weeks, respectively, by regulating the stem cell factor/C-kit pathway. Moreover, the ultrastructure of gallbladder ICCs was significantly altered after 8 weeks, and the protein expression levels of connexin 43 in the gallbladder were differentially altered after 2 and 8 weeks. Finally, cholecystokinin receptor type A (CCK1R) expression in the gallbladder was assessed. In gallbladder ICCs, its expression was significantly increased and decreased after 2 and 8 weeks, respectively. In conclusion, these results demonstrate that the density, ultrastructure and CCK1R expression levels of gallbladder ICCs are differentially altered at various stages of cholesterol cholelithiasis progression, indicating that gallbladder ICCs may be considered a potential therapeutic target for treatment of cholesterol cholelithiasis.

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Section: Discussionmentioning

confidence: 99%

Changes in the interstitial cells of Cajal in the gallbladder of guinea pigs fed a lithogenic diet

Huang

Ding

2021

Exp Ther Med

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“…In particular, a protective role is possible for the hydrophilic bile acid UDCA 194 – 199 . Other therapeutic options (alone or in combination) are promising but not yet supported by strong evidence: statins or inhibitors (or both) of the intestinal absorption of cholesterol such as ezetimibe 79 , 95 , 201 – 207 ; nuclear receptor modulators 99 , 208 – 212 such as 6EUDCA, a synthetic derivative of UDCA acting as FXR modulator 99 , or piperine, an alkaloid able to inhibit ABCG5/8 and LXR expression in the liver reducing biliary cholesterol secretion 100 ; possible modulators of gut microbiota 112 ; dietary/lifestyle models 64 , 65 , 184 , 213 ; pharmacologic agents acting on gallbladder hypomotility 121 , 214 , 215 ; and inflammatory cytokine modulators 216 – 218 .…”

Section: Future Perspectives: From Therapy To Preventionmentioning

confidence: 99%

Recent advances in understanding and managing cholesterol gallstones

Ciaula

Portincasa

2018

F1000Res

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The high prevalence of cholesterol gallstones, the availability of new information about pathogenesis, and the relevant health costs due to the management of cholelithiasis in both children and adults contribute to a growing interest in this disease. From an epidemiologic point of view, the risk of gallstones has been associated with higher risk of incident ischemic heart disease, total mortality, and disease-specific mortality (including cancer) independently from the presence of traditional risk factors such as body weight, lifestyle, diabetes, and dyslipidemia. This evidence points to the existence of complex pathogenic pathways linking the occurrence of gallstones to altered systemic homeostasis involving multiple organs and dynamics. In fact, the formation of gallstones is secondary to local factors strictly dependent on the gallbladder (that is, impaired smooth muscle function, wall inflammation, and intraluminal mucin accumulation) and bile (that is, supersaturation in cholesterol and precipitation of solid crystals) but also to “extra-gallbladder” features such as gene polymorphism, epigenetic factors, expression and activity of nuclear receptors, hormonal factors (in particular, insulin resistance), multi-level alterations in cholesterol metabolism, altered intestinal motility, and variations in gut microbiota. Of note, the majority of these factors are potentially manageable. Thus, cholelithiasis appears as the expression of systemic unbalances that, besides the classic therapeutic approaches to patients with clinical evidence of symptomatic disease or complications (surgery and, in a small subgroup of subjects, oral litholysis with bile acids), could be managed with tools oriented to primary prevention (changes in diet and lifestyle and pharmacologic prevention in subgroups at high risk), and there could be relevant implications in reducing both prevalence and health costs.

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“…These effects are obtained by activating the receptors of ileal liver X receptor α and hepatic farnesoid X receptor [51]. Another study regarding Lidan granules ( Oriental wormwood, Hawthorn fruit, Rice sprout, Germinated barley, Green orange peel, Tangerine peel, Medicated leaves, Cyperus tuber, Radish seed, Caulis perillae, Turmeric root, Rhubarb, Pinellia tube, and Chinese honeylocust fruit ) demonstrated that reducing cholesterol level and increasing bile phospholipid levels by downregulating the expression of inflammatory cytokines are the underlying mechanisms involved in preventing cholelithiasis [52].…”

Section: Potential Mechanisms Underlying the Chc Treatmentsmentioning

confidence: 99%

Mechanisms Underlying the Prevention and Treatment of Cholelithiasis Using Traditional Chinese Medicine

Chen

Zhang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Cholelithiasis is a major public health concern that necessitates highly effective, feasible, and recurrence-preventing therapies. Currently available surgical treatments and medications cannot effectively avoid the recurrence of cholelithiasis. Hence, several Chinese herbal compounds (CHCs) are considered for the treatment of cholelithiasis, considering that they can effectively discharge gallstones and prevent the recurrence of such condition. In the present narrative review, we aim to summarize the underlying mechanisms of currently used CHCs in the treatment of cholelithiasis and to describe the current situation of traditional Chinese medicine (TCM) use for cholelithiasis. Several commonly used CHCs were used to illustrate these issues. We found that the mechanisms underlying the CHC treatments rely on the amelioration of the biliary dynamics factors, maintenance and protection of the liver function, reduction of the cholesterol and bilirubin levels, and regulation of the inflammatory reactions. CHCs as treatments based on TCM can ameliorate the overall bodily function, thereby preventing the recurrence of cholelithiasis. Appropriate application of CHCs would be beneficial for patients and clinicians, although the safety and efficacy of CHCs need further verification.

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Prevention of gallstones by Lidan Granule: Insight into underlying mechanisms using a guinea pig model

Cited by 8 publications

References 25 publications

Changes in the interstitial cells of Cajal in the gallbladder of guinea pigs fed a lithogenic diet

Changes in the interstitial cells of Cajal in the gallbladder of guinea pigs fed a lithogenic diet

Recent advances in understanding and managing cholesterol gallstones

Mechanisms Underlying the Prevention and Treatment of Cholelithiasis Using Traditional Chinese Medicine

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