Berberine for diarrhea in children and adults: a systematic review and meta-analysis

Abstract

Background: Diarrhea is a ubiquitous digestive system disease, leading to loss of fluid and electrolytes, and may be life-threatening, especially in children and adults who are immunosuppressed or malnourished. Berberine has a broad-spectrum antibiotic activity and is very widely used to treat diarrhea in China. No systematic review has been carried out to evaluate the evidence presented in clinical trials. The aim of this study was to assess the effectiveness and safety of berberine in diarrhea treatment among children and adults. Methods: Seven databases and two clinical trial registries were searched on 1 September 2019. Randomized controlled trials were included, where participants were diagnosed (first diagnosed) as having diarrhea according to clear diagnostic criteria. Berberine alone or in combination with Western medication as intervention were included. Subgroup analyses were conducted based on children or adults, acute or persistent diarrhea, infectious or noninfectious and treatment courses. Primary outcomes were clinical cure rate and duration of diarrhea. The GRADE tool was used to assess the quality of evidence. Results: A total of 38 randomized controlled trials were included involving 3948 participants (including 27 trials on 2702 children) were included. Compared with antibiotics, berberine plus antibiotics showed better results in both adults and in children in general, especially when given for 7 days or 3 days in acute infectious diarrhea of children. Compared with the control groups, using berberine alone or in combination with montmorillonite, probiotics, and vitamin B increased the clinical cure rate of diarrhea. The use of berberine alone or berberine combined with montmorillonite reduced the duration of hospitalization. Using berberine had significantly better laboratory indicators (isoenzyme, inflammatory factors, myocardial enzyme, and fecal trait) and fewer systemic symptoms than the no berberine groups. Overall, 22 of 27 trials on children used berberine as an enema. No deaths and serious adverse events were reported. The quality of evidence of included trials was moderate to low or very low. The impact of different dosages, frequencies and treatment durations on the outcomes was not evaluated due to insufficient number of trials. Conclusion: This review demonstrated that berberine was generally effective in improving clinical cure rates and shortening the duration of diarrhea compared with control groups. No severe adverse event was reported. However, there is still a lack of high-quality evidence for evaluating the efficacy and safety of berberine. Trial registration: PROSPERO CRD42020151001 (available from http://www.crd.york.ac.uk/PROSPERO/ ).

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

“…The latter may even be improved due to the higher lipophilicity and thus more balanced bioavailability of the ligands [65]. Accordingly, the activity of these derivatives in the treatment of tuberculosis [7], diarrhea [8], diabetes [9], cardiovascular diseases [10] or high cholesterol levels [11] is worth to be tested, because the parent berberine is already employed as drug for these diseases. In summary, a new complementary class of arylated berberine derivatives was discovered, which may constitute a promising starting point for the development of lead structures in drug discovery.…”

“…Particularly, the latter is established in traditional Chinese medicine as source for anti-inflammatory extracts [2]. Berberine has also been employed in modern medicine because of its antimicrobial [3], antiprotozoal [4], antiviral [5], and anti-inflammatory [6] activity, and it is used in the treatment of tuberculosis [7], diarrhea [8], diabetes [9], cardiovascular diseases [10] or high cholesterol levels [11]. Most interestingly, it has been found that berberine (1a) exhibits a selective cytotoxicity against cancer cells [12,13], which is mainly based on its DNAbinding properties [14].…”

Berberrubine Phosphate: A Selective Fluorescent Probe for Quadruplex DNA

“…of various diseases [35][36][37][38]. Moreover, these compounds exhibit a light-up effect upo binding to polyanionic analytes like DNA, which is, however, rather unselective for th parent berberine [28,33,39,40].…”

“…In fact, many fluorescent light-up probes based on these natural products have been developed that show a highly selective increase in their emission intensity upon binding to G4-DNA [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Among the natural products, berberine and its derivatives are extensively studied substrates because the biocompatibility of this class of compounds has been demonstrated with their application in the treatment of various diseases [ 35 , 36 , 37 , 38 ]. Moreover, these compounds exhibit a light-up effect upon binding to polyanionic analytes like DNA, which is, however, rather unselective for the parent berberine [ 28 , 33 , 39 , 40 ].…”

Capture and Identification of Dual Specificity Mitogen-Activated Protein Kinase Kinase 7 as a Direct Proteomic Target of Berberine to Affect the c-JunN-Terminal Kinase Pathway

“…Berberine (BBR, Figure 1), a Chinese natural product extracted from Coptis chinensis, has been widely used as an over-the-counter (OTC) drug to treat bacterial-caused diarrhea in China for decades. 1 Over the past 20 years, its multiple pharmacological activities have been discovered and elucidated, including antiinflammatory, antitumor, hypoglycemic, hypolipidemic, antivirus, etc, [2][3][4][5][6][7][8][9][10][11] suggesting a typical multitargetdirected mechanism of BBR. A couple of classical cellular pathways, such as NIMA-related kinase 7 (NEK7)/nucleotide-binding domain-like receptor protein 3 (NLRP3) and c-Jun N-terminal protein kinases (JNK)/stress activated protein kinases (SAPKs), as well as interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STATs), 8,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] have been proven to closely account for BBR's polypharmacological effects.…”