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1.
Rev. biol. trop ; 70(1)dic. 2022.
Article in English | LILACS-Express | LILACS, SaludCR | ID: biblio-1387704

ABSTRACT

Abstract Introduction: Pathogenic protozoans, like Entamoeba histolytica and Trichomonas vaginalis, represent a major health problem in tropical countries; and polymeric nanoparticles could be used to apply plant extracts against those parasites. Objective: To test Curcuma longa ethanolic extract and Berberis vulgaris methanolic extracts, and their main constituents, against two species of protozoans. Methods: We tested the extracts, as well as their main constituents, curcumin (Cur) and berberine (Ber), both non-encapsulated and encapsulated in polymeric nanoparticles (NPs), in vitro. We also determined nanoparticle characteristics by photon correlation spectroscopy and scanning electron microscopy, and hemolytic capacity by hemolysis in healthy erythrocytes. Results: C. longa consisted mainly of tannins, phenols, and flavonoids; and B. vulgaris in alkaloids. Encapsulated particles were more effective (P < 0.001); however, curcumin and berberine nanoparticles were the most effective treatments. CurNPs had IC50 values (µg/mL) of 9.48 and 4.25, against E. histolytica and T. vaginalis, respectively, and BerNPs 0.24 and 0.71. The particle size and encapsulation percentage for CurNPs and BerNPs were 66.5 and 73.4 nm, and 83.59 and 76.48 %, respectively. The NPs were spherical and significantly reduced hemolysis when compared to non-encapsulated extracts. Conclusions: NPs represent a useful and novel bioactive compound delivery system for therapy in diseases caused by protozoans.


Resumen Introducción: Los protozoos patógenos, como Entamoeba histolytica y Trichomonas vaginalis, representan un importante problema de salud en los países tropicales; y se podrían usar nanopartículas poliméricas para aplicar extractos de plantas contra esos parásitos. Objetivo: Probar los extractos etanólicos de Curcuma longa y Berberis vulgaris, y sus principales constituyentes, contra dos especies de protozoos. Métodos: Probamos los extractos, así como sus principales constituyentes, curcumina (Cur) y berberina (Ber), tanto no encapsulados como encapsulados en nanopartículas poliméricas (NPs), in vitro. También determinamos las características de las nanopartículas por espectroscopía de correlación de fotones y microscopía electrónica de barrido, y la capacidad hemolítica por hemólisis en eritrocitos sanos. Resultados: C. longa tenía principalmente: taninos, fenoles y flavonoides; y B. vulgaris, alcaloides. Las partículas encapsuladas fueron más efectivas (P < 0.001); sin embargo, las nanopartículas de curcumina y berberina fueron los tratamientos más efectivos. CurNPs tenía valores IC50 (µg/mL) de 9.48 y 4.25, contra E. histolytica y T. vaginalis, respectivamente, y BerNPs 0.24 y 0.71. El tamaño de partícula y el porcentaje de encapsulación para CurNPs y BerNPs fueron: 66.5 y 73.4 nm, y 83.59 y 76.48 %, respectivamente. Los NP son esféricos y redujeron significativamente la hemólisis en comparación con los extractos no encapsulados. Conclusiones: Las NP representan un sistema de administración de compuestos bioactivos útil y novedoso para la terapia enfermedades causadas por protozoos.


Subject(s)
Trichomonas vaginalis , Berberis vulgaris , Curcuma , Entamoeba histolytica
2.
Article in Chinese | WPRIM | ID: wpr-928342

ABSTRACT

OBJECTIVE@#To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).@*METHODS@#Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation.@*RESULTS@#The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01).@*CONCLUSION@#Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.


Subject(s)
Animals , Berberine/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Plates , Cartilage, Articular , Humans , Ligands , Male , NF-kappa B/metabolism , Osteoarthritis/metabolism , Osteoprotegerin/metabolism , RNA, Messenger/therapeutic use , Rabbits
3.
Acta Pharmaceutica Sinica ; (12): 1263-1272, 2022.
Article in Chinese | WPRIM | ID: wpr-924738

ABSTRACT

Berberine is a naturally occurring benzylisoquinoline alkaloid with a wide range of pharmacological activities, such as antibacterial, anticancer, hypolipidemic, antidiabetic and antidiarrheal. Although berberine has a wide range of curative effects, the extremely low bioavailability (< 1%) limits its clinical application. Pure berberine preparations have not yet been approved for any specific disease. The low oral bioavailability of berberine is mainly due to poor solubility caused by self-aggregation under acidic conditions, low permeability, P-glycoprotein (P-gp)-mediated efflux, and liver and intestine metabolism. To improve the oral bioavailability of berberine, researchers have adopted a variety of strategies, including the application of various nano-delivery systems, penetration enhancers and P-gp inhibitors, structural modifications, and development of berberine derivatives. Improving the oral bioavailability of berberine can improve the pharmacological activity of berberine, reduce the dosage, and then reduce the toxic and side effects. This review summarized the various pharmacological activities, metabolism progress and pharmacokinetic characteristics of berberine, the newly discovered berberine target intestinal microbiota and focused on the strategies to improve the oral bioavailability of berberine by improving solubility and permeability, inhibiting P-gp efflux, and structural modification. The research on berberine was prospected, which provided guidance for the in-depth study of berberine.

4.
Acta Pharmaceutica Sinica ; (12): 343-352, 2022.
Article in Chinese | WPRIM | ID: wpr-922910

ABSTRACT

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

5.
Braz. J. Pharm. Sci. (Online) ; 58: e18835, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374544

ABSTRACT

Abstract The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential.

6.
Braz. j. med. biol. res ; 55: e12096, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374702

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is considered to be a manifestation of hepatic metabolic syndrome. Some studies on the pathogenesis of NAFLD by targeting gut microbiota have attracted wide attention. Previous studies have demonstrated the positive effects of berberine and evodiamine on metabolic diseases and gut microbiota dysbiosis. However, it is not known whether the combination of berberine and evodiamine (BE) can prevent the development of high-fat diet (HFD)-induced NAFLD. Therefore, we aimed to explore the protective effects of BE on the development of HFD-induced NAFLD from the perspective of the gut microbiota. Gut microbiota profiles were established by high throughput sequencing of the bacterial 16S ribosomal RNA gene. The effects of BE on liver and intestinal tissue, intestinal barrier integrity, and hepatic inflammation were also investigated. The results showed that the abundance and diversity of gut microbiota were enriched by BE treatment, with an increase in beneficial bacteria, such as Lactobacillus, Ruminococcus, and Prevotella, and a decrease in pathogenic bacteria such as Fusobacterium and Lachnospira. In addition, BE effectively improved liver fat accumulation and tissue damage, inhibited the apoptosis of intestinal epithelial cells, increased the contents of intestinal tight junction proteins, and decreased the expression of pro-inflammatory factors. Consequently, BE treatment could be an effective and alternative strategy for alleviating NAFLD by modulating gut microbiota and safeguarding the intestinal barrier.

7.
Article in English | WPRIM | ID: wpr-922534

ABSTRACT

OBJECTIVE@#The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs).@*METHODS@#SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na@*RESULTS@#Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by downregulating the B-cell lymphoma 2 (Bcl-2) expression rate and upregulating the Bcl-2-associated X protein and caspase-3 expression rates. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group.@*CONCLUSION@#Our study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.


Subject(s)
Animals , Antineoplastic Agents , Antioxidants , Berberine , Male , Mice , Nanoparticles , Selenium
8.
Chinese Journal of Hepatology ; (12): 224-229, 2022.
Article in Chinese | WPRIM | ID: wpr-935931

ABSTRACT

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.


Subject(s)
Animals , Berberine/therapeutic use , Fatty Liver , Male , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , Necrosis
9.
Article in Chinese | WPRIM | ID: wpr-933502

ABSTRACT

Objective:To evaluate the in vitro antifungal activity of berberine against Talaromyces marneffei (TM) in yeast phase. Methods:There were 21 TM strains, including l standard strain (ATCC22019), 10 clinical isolates and 10 isolates from wild bamboo rats. TM strain suspensions at a concentration of (1 - 5) × 10 3 colony-forming units/ml were incubated in microdilution plates containing difierent concentrations of berberine, fluconazole, itraconazole, voriconazole, amphotericin B or caspofungin at 37 ℃ for 48 hours. Meanwhile, the wells containing only culture media and TM strains but without antifungal drugs served as the positive control group, and those containing only culture media served as the negative control group. The minimum inhibitory concentrations (MICs) of antifungal drugs against TM yeasts were determined according to the Clinical and Laboratory Standards Institute (CLSI) broth microdilution susceptibility method (M27-A3 document) . Results:The MICs of the above antifungal drugs were all within the reference ranges for the quality control strain (ATCC22019), and TM strains grew well in the positive control wells. The MIC ranges of berberine, itraconazole, voriconazole, amphotericin B and caspofungin against TM strains were 32 - 64 mg/L, 0.06 - 0.125 mg/L, 0.06 - 0.125 mg/L, 1 - 2 mg/L and 16 - 32 mg/L respectively; the MIC range of fluconazole was 2 - 4 mg/L for non-resistant strains, and 128 mg/L for fluconazole-resistant clinical strains.Conclusion:Berberine exhibits antifungal activity against TM in yeast phase.

10.
Article in Chinese | WPRIM | ID: wpr-933395

ABSTRACT

Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.

11.
Article in Chinese | WPRIM | ID: wpr-930175

ABSTRACT

Objective:To observe the effect of berberine on leukemia drug-resistant cell strain K562/A02 to Adriamycin resistance and protein kinase C-alpha (PRKCA) and explore its possible mechanism.Methods:The leukemia K562 cells of human chronic myeloid and Adriamycin resistant strain K562/A02 were cultured in vitro with 2.5-50.0 μmol/L doxorubicin to treat thoese cells and drug resistance of K562 and K562/A02 to Adriamycin was detected, the 50% inhibitory concentration (IC 50) of the drug was calculatedthe resistance of K562 and K562/A02 to doxorubicin was detectd , and, K562/A02 cells were treated with doxorubicin solution at a final concentration of 5 μmol/L, and K562/A02 cells were divided into control group, inhibitor group (50 μmol/L PRKCA inhibitor), low dose berberine group, medium dose berberine group and high dose berberine group. Cell counting (CCK-8) method was used to detect the inhibition rate of cell proliferation, the apoptosis was detected by flow cytometry, real-time fluorescent quantitative PCR assay detects PRKCA, MRP, multidrug resistance related genes (MDR1) levels, and the protein expressions of protein kinase C-α (PRKCA), multidrug resistance related protein (MRP), P-glycoprotein (P-gp) were detected by Western blotting. Results:The IC 50 concentration of K562/A02 to Adriamycin was significantly higher than K562. Compared with the control group, the inhibition rate of cell proliferation and the apoptosis rate in the inhibitor group, low-dose berberine group, medium-dose berberine group, and high-dose berberine group were significantly increased ( P<0.05), the expression of PRKCA mRNA (0.45±0.08, 0.92±0.10, 0.57±0.05, 0.35±0.04 vs. 1.00±0.12), MDR1 gene (0.73±0.08, 0.87±0.09, 0.65±0.07, 0.41±0.05 vs. 1.00±0.11) and PRKCA (0.59±0.09, 0.78±0.12, 0.61±0.11, 0.42±0.07 vs. 0.96±0.14), MRP (0.62±0.08, 0.79±0.13, 0.62±0.10, 0.41±0.06 vs. 0.98±0.14), P-gp (0.55±0.08, 0.75±0.12, 0.59±0.09, 0.35±0.06 vs. 0.92±0.15) were significantly reduced ( P<0.05), and berberine was dose-dependent ( P<0.05); Overexpression of PRKCA can inhibit the effect of berberine on reversing the drug resistance of K562/A02 cells. Conclusion:Berberine may reverse the drug resistance of K562/A02 to Adriamycin by down-regulating PRKCA.

12.
Acta Pharmaceutica Sinica B ; (6): 92-106, 2022.
Article in English | WPRIM | ID: wpr-929283

ABSTRACT

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

13.
Article in Chinese | WPRIM | ID: wpr-941024

ABSTRACT

OBJECTIVE@#To explore the mechanism by which berberine inhibits ferroptosis of mouse hippocampal neuronal cells (HT22).@*METHODS@#Cultured HT22 cells were pretreated with 30 or 60 μmol/L berberine for 2 h before exposure to 0.5 μmol/L erastin for 8 h, and the cell proliferation, intracellular ferric iron level, changes in intracellular reactive oxygen species (ROS) and cell apoptosis were detected using CCK-8, Fe2+ fluorescent probe, fluorescent dye (DAPI) and fluorescent probe (H2DCFH-DA). RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of Nrf2, HO-1 and GPX4 in the cells. We further tested the effects of treatments with 2 μmol/L ML385 (a Nrf2 inhibitor), 60 μmol/L berberine and erastin in the cells to explore the protective mechanism of berberine against erastin-induced ferroptosis in the neuronal cells.@*RESULTS@#Treatment with 0.5 μmol/L erastin significantly lowered the viability of HT22 cells (P < 0.05) and increased the production of ROS, cell apoptosis rate and ferric iron level (P < 0.05). Pretreatment with 30 and 60 μmol/L berberine both significantly increased the vitality of erastin-exposed cells (P < 0.05) and lowered the levels of intracellular ROS and ferric iron content (P < 0.05). RT-qPCR and Western blotting showed that berberine obviously promoted the expressions of Nrf2, HO-1 and GPX4 in the cells (P < 0.05), and treatment with ML385 significantly inhibited the Nrf2-HO-1/GPX4 pathway, increased intracellular ROS and ferric iron contents and mitigated the protective effect of berberine against erastin-induced ferroptosis (P < 0.05).@*CONCLUSION@#Berberine can inhibit erastin-induced ferroptosis in HT22 cells possibly by activating the Nrf2-HO-1/ GPX4 pathway.


Subject(s)
Animals , Berberine/pharmacology , Ferroptosis , Fluorescent Dyes , Hippocampus/metabolism , Iron/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Piperazines , Reactive Oxygen Species/metabolism
14.
Article in Chinese | WPRIM | ID: wpr-940664

ABSTRACT

ObjectiveTo investigate the efficacy and mechanism of berberine hydrochloride (BBH) against lung cancer cells through the mevalonate (MVA) pathway. MethodHuman lung cancer A549 cells and mouse Lewis lung carcinoma (LLC) cells were used as research subjects. Cell proliferation and cell counting kit-8 (CCK-8) assay were performed to detect the inhibitory effect of BBH (10, 20, 30, 40, 50 μmol·L-1) on the proliferation of the two kinds of cells (48 h). Then cell scratch assay was used to explore the influence of BBH (40 μmol·L-1) on the migration of A549 and LLC cells (24, 48 h), and colony formation assay was conducted to compare the colony formation ability of the cells under different concentrations of BBH (10, 20, 40 μmol·L-1). Moreover, the effects of BBH (40 μmol·L-1) on the content of acetyl-coenzyme A (A-CoA) and total cholesterol (TC) in A549 and LLC cells were determined by kit assay. AutoDock Vina was used for the dock of BBH and MVA pathway regulatory protein, sterol regulatory element-binding protein 2 (SREBP2). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to observe the effects of BBH (40 μmol·L-1) on the mRNA expression of nine genes related to the MVA pathway in A549 and LLC cells: hydroxymethylglutaryl-CoA synthase 1 (HMGCS1), hydroxymethylglutaryl-CoA Reductase (HMGCR), mevalonate kinase (MVK), phosphomevalonate kinase (PMVK), mevalonate 5-pyrophosphate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), squalene epoxidase (SQLE), farnesyl-diphosphate farnesyltransferase 1 (FDFT1), and geranylgeranyl diphosphate synthase 1 (GGPS1). Western blot was performed to clarify the effects of BBH (40 μmol·L-1) on the expression of three key proteins of the MVA pathway: HMGCS1, HMGCR, and FDFT1. The Cancer Genome Atlas (TCGA) database was searched to analyze the relationship between HMGCS1, HMGCR, FDFT1 and transcription gene SREBF2 in non-small cell lung cancer (NSCLC). ResultCompared with the conditions in the control group, the proliferation, migration, and colony formation of A549 and LLC cells in the BBH group were decreased (P<0.01), while the cell apoptosis rate was increased (P<0.01). Molecular docking showed that BBH had good binding activity with SREBP2. In addition, the content of A-CoA and TC of the MVA pathway was reduced (P<0.01). BBH down-regulated the mRNA expression of HMGCS1, HMGCR, MVK, PMVK, MVD, FDPS, SQLE, FDFT1, and GGPS1 in A549 and LLC cells (P<0.01), and lowered the levels of HMGCS1, HMGCR, and FDFT1 proteins (P<0.05, P<0.01). In NSCLC patients, HMGCS1, HMGCR, and FDFT1 were highly correlated with SREBF2 (R=0.54, R=0.57, and R=0.48). ConclusionBBH can inhibit the proliferation, migration, and colony formation of A549 and LLC cells and promote cell apoptosis, which may be related to the regulation of MVA pathway by BBH binding to SREBP2.

15.
Article in Chinese | WPRIM | ID: wpr-940661

ABSTRACT

ObjectiveTo investigate the synergistic effect of Coptidis Rhizoma crude polysaccharide (CCP) and berberine (BBR) in treating ulcerative colitis (UC) model mice. MethodThirty male BALB/c mice were randomized into five groups. Except the 6 mice in the normal group, the rest were given 5% dextran sodium sulfate in their daily drinking water to establish the UC model. After modeling, the mice were administrated with corresponding agents by gavage once daily for 4 days: BBR (100 mg·kg-1) group, BBR (100 mg·kg-1) + low-dose (22.8 mg·kg-1) CCP group, BBR (100 mg·kg-1) + high-dose (45.6 mg·kg-1) CCP group. The mice in the model group and normal group were administrated with the same volume of normal saline. At the end of the experiment, the mice were sacrificed for the collection of colon, and the expression of tight junction proteins zonula occluden-1 (ZO-1), Claudin-1, and Occludin in colon tissue was detected by Western blot. With the normal group as the control, the disease activity index (DAI) score, colon length, colon histomorphology, and expression levels of tight junction proteins in other groups were evaluated. ResultCompared with the normal group, the modeling down-regulated the protein levels of ZO-1, Claudin-1, and Occludin (P<0.01). Compared with the model group, BBR did not significantly change the protein level of Claudin-1 and up-regulated those of ZO-1 and occludin (P<0.01). The expression levels of Claudin-1, ZO-1, and Occludin were up-regulated in BBR + CCP groups (P<0.01). The expression levels of tight junction proteins in BBR + CCP groups were significantly higher than those in the BBR group (P<0.05). ConclusionThe administration of CCP combined with BBR can effectively ameliorate intestinal mucosal barrier damage in the mice with UC.

16.
Article in Chinese | WPRIM | ID: wpr-940294

ABSTRACT

ObjectiveOn the basis of determining the protective effect of berberine (BBR) on cerebral ischemia, crucial transcription factors (TFs) of BBR against cerebral ischemia was identified by using transcriptome and proteome sequencing. MethodThe model of middle cerebral artery occlusion (MCAO) was established by thread embolization. The sham operation group, model group, low-dose group of BBR (dose of 37.5 mg·kg-1·d-1) and high-dose group of BBR (75 mg·kg-1·d-1) were set up. The rats were killed after continuous intragastric administration for 7 days. The pharmacodynamics was evaluated by Longa score and cerebral infarction rate, and the expressions of inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). Then, RNA-Seq technique was used to detect the differentially expressed genes (DEGs) before and after BBR intervention, and DAVID 6.8 was used for enrichment analysis of DEGs. CatTFREs technique was used to detect differential TFs before and after BBR intervention, and DAVID 6.8 and STRING 11.0 were used for enrichment analysis and TFs association analysis. Finally, by integrating the activity of TFs and the changes of downstream target genes, crucial TFs were identified and the related regulatory network was constructed by Cytoscape 3.7.1. ResultCompared with the sham operation group, the neurological impairment was significant in the model group (P<0.01), and compared with the model group, the low and high dose BBR groups could significantly reduce the neurological function damage (P<0.01) and decrease the rate of cerebral infarction (P<0.01). Transcriptome data analysis showed that BBR was involved in the recovery process after cerebral ischemia mainly by affecting cell adhesion, brain development, neuron migration, calcium signaling pathway, cyclic adenosine monophosphate (cAMP) signaling pathway, inflammatory response and other related functions and signaling pathways. Proteomic data analysis showed that the differentially expressed TFs after BBR intervention interfered with cerebral ischemia mainly by regulating cell differentiation, immune system process, cell proliferation and other biological processes. In addition, integration analysis of TFs and DEGs revealed that transcription factor CP2-like 1 (TFCP2L1), nuclear factor erythroid-2 like 1 (NFE2L1), neurogenic differentiation protein 6 (NeuroD6) and POU domain, class 2, transcription factor 1 (POU2F1) were crucial TFs against cerebral ischemia-reperfusion injury mediated by BBR. ConclusionBBR has obvious protective effect on cerebral ischemia-reperfusion injury and its crucial TFs include TFCP2L1, NFE2L1, NeuroD6 and POU2F1.

17.
Article in Chinese | WPRIM | ID: wpr-907150

ABSTRACT

Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.

18.
Article in Chinese | WPRIM | ID: wpr-907048

ABSTRACT

@#Berberine is a natural isoquinoline alkaloid extracted from Rhizoma Coptidis and other Chinese herbal medicines. Since berberine has a variety of biological effects, such as bacteriostasis, anti-inflammatory, anti-bone resorption and blood sugar-lowering effects, and is associated with few side effects, studies are increasingly discovering its potential application in the prevention and treatment of periodontitis. This review summarizes the relevant research progress of berberine in the prevention and treatment of periodontitis in recent years, aiming to provide a new strategy for the clinical prevention and treatment of periodontitis. The results of the literature review showed that berberine could prevent the occurrence and development of periodontitis by inhibiting periodontal pathogens, reducing periodontal tissue inflammation and inhibiting alveolar bone resorption. However, the mechanism of periodontitis is complicated, and current research remains limited. In the future, more in vivo and in vitro studies are needed to further explore the mechanism of berberine in inhibiting the occurrence and development of periodontitis, and more large-sample prospective clinical studies should be conducted to confirm the effect of berberine on the prevention and treatment of periodontitis.

19.
Acta Pharmaceutica Sinica B ; (6): 1789-1812, 2021.
Article in English | WPRIM | ID: wpr-888835

ABSTRACT

Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

20.
Article in Chinese | WPRIM | ID: wpr-888081

ABSTRACT

The present study aims to investigate the effects of the main components(aesculin, berberine hydrochloride, and anemoside B4) in the butyl alcohol extract of Baitouweng Decoction(BAEB) on the chemotaxis of neutrophils induced by dimethyl sulfoxide(DMSO). HL60 cells were cultivated in RPMI-1640 complete medium, and transferred into a 6-well plate(2 × 10~5 per mL) with 4 mL in each well, followed by incubation with DMSO at 1.3% for five days. The morphologic changes of cells were observed under an inverted microscope. The CD11 b expression after DMSO induction was analyzed by flow cytometry. The effects of aesculin, berberine hydrochloride, and anemoside B4 on the cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The effects of the main components on the production and polarization of F-actin protein were also examined by flow cytometry and laser confocal microscopy. PI3 K/Akt signaling pathway was checked by Western blot. As revealed by the results, neutrophil-like HL60 cells were observed after DMSO induction. The CD11 b expression in these cells increased significantly as indicated by the flow cytometry. Additionally, 100 μg·mL~(-1) aesculin, 8 μg·mL~(-1) berberine hydrochloride, and 80 μg·mL~(-1) anemoside B4 were potent in inhibiting the migration of neutrophils and reducing F-actin expression. Berberine hydrochloride was verified to be capable of diminishing phosphorylated PI3 K/Akt protein expression. The findings indicate that aesculin, anemoside B4, and especially berberine hydrochloride in the BAEB can inhibit the chemotaxis of neutrophils, which is possibly achieved by the inhibition of F-actin and PI3 K/Akt signaling pathway.


Subject(s)
1-Butanol , Berberine/pharmacology , Chemotaxis , Drugs, Chinese Herbal/pharmacology , Neutrophils
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