Berberine Research Articles

Nanoparticles of ZnO/Berberine complex contract COVID-19 and respiratory co-bacterial infection in addition to elimination of hydroxychloroquine toxicity.

PurposeA novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy.MethodsFirst, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs.ResultsThe results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo.ConclusionThe ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo.

Galactosylated nanoconstructs of Berberine with enhanced Biopharmaceutical and cognitive potential: A preclinical evidence in Alzheimer ‘s disease

Numerous oral treatment options have been reported for neurological diseases, particularly Alzheimer's disease (AD). Berberine (BRB), a promising phytoactive drug, has been successfully explored for effective therapeutic management of AD and other neurodegenerative disorders. However, it poses formidable challenges of exceedingly poor oral bioavailability of 0.68%, primarily owing to its poor intestinal permeation, extremely low aqueous solubility, and extensive P-glycoprotein efflux transport. The present studies, accordingly, were undertaken to develop the galactose-tethered nanostructured lipidic carriers of BRB for efficient brain uptake. NLCs were systematically developed and optimized using QbD paradigms, and thoroughly characterized for particle size, zeta potential, morphology, entrapment efficiency and in vitro drug release. U-87 cell lines studies indicated augmentation in cellular permeability and uptake of the galactosylated NLCs. Oral bioavailability was found to be highly significantly enhanced with over 8.21-folds and 3.56-folds (p < 0.001 each) improvement in the values of AUC48h and Cmax, respectively, along with substantial elevation in brain drug levels too (p < 0.05 to p < 0.001). Also, tmax was found to be notably increased by 1.41-folds (p < 0.05), indicating extended release characteristics of the galactosylated NLCs. Studies on brain homogenates exhibiting distinctly superior biochemical parameters, and behavioural studies demonstrating marked cognitive potential in β-amyloid treated rats further substantiated their promising utility in the management of AD. High degree of Level A linear correlations were established between fractions of drug dissolved (in vitro) and of drug absorbed (in vivo) BRB and its NLC formulations. Stability studies at 5 °C indicated robustness of galactosylated NLCs for 6 months. The current preclinical findings, accordingly, offer distinctive potential of the developed NLCs in enhanced drug efficacy, extended duration of action and effective therapeutic management of AD.

Oral administration of berberine represses macrophage activation-associated benign prostatic hyperplasia: a pivotal involvement of the NF-κB

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in men over the age of 50. Clinical studies have suggested that chronic inflammation is associated with BPH pathoprogression. Berberine (BB) is a natural compound found in Berberis vulgaris, Coptis chinensis and Phellodendron amurense. Although several studies have documented that BB may be effective for inflammation, the effects of the oral administration of BB on BPH are not fully understood. The effects of BB on chronic prostatic inflammation were evaluated in a testosterone-induced BPH animal model. Orally administered BB alleviated the pathological alterations induced by BPH and significantly suppressed the expression of inflammatory markers while enhancing the expression of antioxidant factors. Furthermore, BB regulated the activation of macrophages via NF-κB signaling pathway inhibition in the BPH rat model. The effects and underlying signaling pathway of BB in RWPE-1 cells exposed to macrophage conditioned medium (CM) were also demonstrated in vitro. While CM stimulation induced prostatic cell proliferation and upregulated the expression of inflammatory factors, BB exerted anti-proliferation and anti-inflammatory effects in RWPE-1 cells. These findings propose that BB suppresses androgen-dependent BPH development by targeting NF-κB-mediated pro-inflammatory signaling.

Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat's Brain.

Chemotherapy-associated neurotoxicity is one of the principal side-effects for doxorubicin (DOX)-treated cancer patients. Despite its poor-penetration across the blood-brain barrier (BBB), DOX is linked to the induction of oxidative stress and neuroinflammation. Berberine (BEB) is a natural polyphenolic alkaloid, which exhibits unique antioxidant activity and anti-inflammatory potential. The present study was performed to investigate the neuroprotective potential of BEB in a rodent model of DOX-induced neurotoxicity. Neurotoxicity was induced in rats via a single acute dose of DOX (20mg/kg/week, i.p.). BEB was administered at 50mg/kg/day orally for 10days before and 4days after DOX administration. Brain acetylcholinesterase (AChE) activities were evaluated. Oxidative stress was investigated via the colorimetric determination of lipid peroxides, glutathione reduced (GSH) contents and catalase (CAT) activities in the brain tissue. In addition, DOX-induced genotoxicity was evaluated using comet assay. DOX produced a significant elevation in AChE activities. Additionally, DOX provoked oxidative stress as evidenced from the significant elevation in lipid peroxidation along with depletion in GSH contents and CAT activities. Moreover, DOX resulted in neuroinflammation as indicated by the elevation of pro-inflammatory mediator glial fibrillary acid protein (GFAP), as well as, the pro-apoptotic nuclear factor kappa B (NF-κB) and caspase-3 in brain tissue. Co-treatment with BEB significantly counteracted DOX-induced oxidative stress, neuroinflammation and genotoxicity. Histopathological and immunohistochemical examination supported the biochemical results. BEB demonstrated neuroprotective potential through exerting cholinergic, anti-oxidative, genoprotective, anti-inflammatory, and anti-apoptotic activities. Our findings present BEB as a promising "pre-clinical" neuroprotective agent against DOX-induced neurotoxicity during anti-neoplastic therapy.

Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice

BackgroundThe combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD.ResultsDEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathwaysConclusionDEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.Graphic abstract

The protective impact of berberine against doxorubicin-induced nephrotoxicity in rats

Doxorubicin (DOX) is a well-known anti-neoplastic agent that is widely employed to treat several types of malignancies. The current study was designed to investigate the renoprotective potential of berberine (BEB) on the doxorubicin (DOX)-induced nephrotoxicity and renal fibrosis. Rats were allocated into four groups; Negative Control, DOX nephrotoxic-induced group received a single dose of DOX (20 mg/kg, i.p.), BEB-group received (50 mg/kg, p.o.) for 14 days, and co-treatment group BEB + DOX where rats were pre-treated with BEB for 10 successive days, then received a single dose of DOX on the 11th day, followed by 4 days of receiving BEB. DOX resulted in nephrotoxicity manifested by significant increments in urea, creatinine, and kidney injury molecule (KIM-1), these biochemical findings were supported with the histopathological lesions in renal tissues. Moreover, DOX provoked oxidative stress through enhancing renal malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, and decreased renal catalase (CAT) activity. DOX triggered renal fibrosis represented by increased transforming growth factor beta-1 (TGF-β1) and elevated collagen deposition. DOX stimulated apoptosis and inflammation in renal tissues as confirmed by increased immunoexpression of caspase-3 and NF-κB, respectively. These effects were alleviated by BEB co-treatment. Co-treatment with BEB markedly prohibited DOX-induced oxidative damage, inflammation, apoptosis, and fibrosis in renal tissue. Histopathological and immunohistochemical investigations showed the nephroprotective potential of BEB on renal injury, which was consistent with the biochemical findings. Accordingly, it could be concluded that the nephroprotective potential of BEB against DOX-induced kidney injury and fibrosis might be mediated by the anti-oxidant, anti-inflammatory and anti-fibrosis activities.

Probing Synergistic Targets by Natural Compounds for Hepatocellular Carcinoma.

BackgroundDesigning combination drugs for malignant cancers has been restricted due to the scarcity of synergy-medicated targets, while some natural compounds have demonstrated potential to enhance anticancer effects.MethodsWe here explored the feasibility of probing synergy-mediated targets by Berberine (BER) and Evodiamine (EVO) in hepatocellular carcinoma (HCC). Using the genomics-derived HCC signaling networks of compound treatment, NF-κB and c-JUN were inferred as key responding elements with transcriptional activity coinhibited during the synergistic cytotoxicity induction in BEL-7402 cells. Then, selective coinhibitors of NF-κB and c-JUN were tested demonstrating similar synergistic antiproliferation activity.ResultsConsistent with in vivo experiments of zebrafish, coinhibitors were found to significantly reduce tumor growth by 79% and metastasis by 96% compared to blank control, accompanied by anti-angiogenic activity. In an analysis of 365 HCC individuals, the low expression group showed significantly lower malignancies and better prognosis, with the median survival time increased from 67 to 213%, compared to the rest of the groups.ConclusionTogether, NF-κB and c-JUN were identified as promising synergistic inducers in developing anti-HCC therapies. Also, our method may provide a feasible strategy to explore new targeting space from natural compounds, opening opportunities for the rational design of combinational formulations in combatting malignant cancers.

Bilayer Membrane Composed of Mineralized Collagen and Chitosan Cast Film Coated With Berberine-Loaded PCL/PVP Electrospun Nanofiber Promotes Bone Regeneration.

Bone defects are difficult to repair and reconstruct as bone regeneration remains technically challenging, with exogenous factors required to accelerate this process. Biodegradable synthetic scaffolds are promising materials for stimulating bone tissue repair. In this study, we investigated whether a bilayer membrane that includes mineralized collagen (MC) and chitosan (CS) delivering berberine (BER)—a typical Chinese herbal monomer—could promote bone healing in a rat model. An MC/CS cast film was coated with polycaprolactone (PCL)/polyvinylpyrrolidone (PVP) electrospun nanofibers loaded with BER, yielding the BER@PCL/PVP-MC/CS bilayer membrane. The 3-dimensional structure had nanofibers of uniform diameter and showed good hydrophilicity; the bilayer membrane showed favorable mechanical properties. BER@PCL/PVP-MC/CS enhanced the proliferation and attachment of MC3T3-E1 cells in vitro and induced bone regeneration when implanted into a rat femoral bone defect. These findings provide evidence that BER@PCL/PVP-MC/CS has clinical potential for effective bone repair.

Novel Inhibitors of an Insect Pest Chitinase: Design and Optimization of 9-O-Aromatic and Heterocyclic Esters of Berberine.

OfChi-h, a lepidopteran-exclusive glycoside hydrolase family 18 (GH18) chitinase from the agricultural insect pest Ostrinia furnacalis, is a promising molecular target candidate for pest control and management. Berberine (BER), a traditional Chinese medicine, binds to a wide variety of glycosyl hydrolases via an identical mechanism, showing potential as a pesticide lead compound. In this work, we found that BER was a moderate inhibitor of OfChi-h with a Ki of 16.1 μM. To improve its efficacy, a series of BER derivatives featuring an ester bond linked to an aromatic or heterocyclic aromatic ring at the 9-position were designed and evaluated as effective OfChi-h inhibitors. The most potent compound, compound 19e with a nicotinate group, exhibited a Ki of 0.093 μM. Molecular docking analysis suggested that the common binding mode of BER derivatives featured a network of π-π stacking and electrostatic interactions and that the group at the 9-position enhanced the van der Waals and hydrogen bonding interactions. Administration of the BER derivative 19c to 4th-instar O. furnacalis larvae in an artificial diet led to their impaired growth and metamorphosis. This work provides a new starting point for the modification of BER for use in pest control.

The effect of Berberine on obesity through browning of the inguinal white adipose tissue of male rats

Background: Obesity increases the risk of many diseases. White adipose tissue (WAT) browning is being targeted in the treatment of obesity. Berberine (BR) is a plant alkaloid, used mainly in treatment of diarrhea. Studies revealed that BR improves some metabolic disorders in obese but the browning effect of BR on WAT is not fully investigated.Aim of the work: Testing the possible impact of BR on browning of inguinal WAT (iWAT) of adult male albino rats, and to study its possible ameliorating effect on the obesity associated disturbed lipid profile.Materials and methods: Forty-eight adult male albino rats were divided into two main groups; normally fed diet group (NFD) and high fat diet group (HFD). Normal fat diet group was subdivided into three subgroups. Normal fat diet control group (NFDc) received no treatment. Normal fat diet-berberine low dose (NFD+BRL) group received 5mg/kg body weight (b.w) BR, and normal fat diet-berberine high dose (NFD+BRH) group received 10mg/kg b.w berberine. High fat diet group was subdivided into three subgroups: High fat diet control group (HFDc), high fat diet-berberine low dose (HFD+BRL) group and high fat diet-berberine high dose (HFD+BRH) group. Results: Berberine promoted adipocyte browning in the iWAT, where the beige adipocytes were revealed. In addition, browning markers expression in iWAT; UCP1, PGC-1α and CIDEA increased. Also, BR ameliorated the disturbed lipid profile in HFD group.Conclusion: Berberine showed to be a safe browning agent which also improved the dyslipidemia occurred in HFD group. Berberine high dose showed better results than the lower dose. Thus, we believe that BR has excellent potential as an effective safe anti-obesity agent.

Exploring the synergistic mechanism of Gegen Qinlian Decoction on the Wnt signaling pathway using an integrated strategy of network pharmacology and RNA-seq

Ethnopharmacological relevanceGegen Qinlian Decoction (GQD) (including: Puerariae lobatae (Willd.) Ohwi, radix; (short for Gengen) Glycyrrhiza uralensis Fisch., root and rhizome (short for Gancao), honeyed; Coptis chinensis Franch., rhizome (short for Huanglian); Scutellaria baicalensis Georgi, radix, boiled (short for S. baicalensis) has been widely used to treat inflammatory bowel disease (IBD) and colorectal cancer (CRC). To explore compatibility mechanism of GQD could be of advantage to investigate the complex principle of TCM, which might be conducive to the exploration of the modernization of TCM. Aim of reviewIn this study, a strategy based on system pharmacology was constructed to uncover the multi-target regulation and compatibility mechanism of GQD on the Wnt signaling pathways. Material and methodsThe pharmacological network of GQD was constructed by TCMSP, DAVID, Uniprote database. The cell growth inhibitory effects of puerarin (PUE), wogonin (WOG), berberine (BER), and glycyrrhetinic acid (GLY) on SW480 cells were assessed using CCK-8 assay. The multi-target regulation and compatibility mechanism of combination PUE with GLY were examined by RNA-seq, HPLC-QQQ/MS, qRT- PCR and Western blot analysis. ResultsNetwork pharmacology analysis indicated that PUE, WOG, BER and GLY were the active components in GQD and had a synergistic effect on the targets of the Wnt signaling pathway. Additionally, pharmacological experiments revealed that WOG, BER, and GLY inhibited activity of colorectal cancer (CRC) cell lines SW480 cells, and that PUE only exhibited effective antitumour activity when combined with GLY. CTNNB1, CCND1 and SMAD4 were identified as synergistic targets inhibited by PUE-GLY. Moreover, PUE-GLY could influence the Wnt signaling pathway by upregulating GSK3B and downregulating CTNNB1 synergistically. It also showed that GLY could effectively increase the intracellular content of PUE based on HPLC-QQQ/MS analysis, and this process was achieved by influencing the targets of the membrane's pathway, such as cell adhesion molecules, focal adhesion, and tight junctions. ConclusionGLY was revealed a multi-target mechanism, which could downregulate CTNNB1 as the active component and intervene in membrane proteins (CDH1, CADM1, ITGB2, ICAM1, ITGA1) as ‘guide’ in the formulae. Moreover, the mechanism of synergistic antitumour action of PUE (the active component of Monarch drug) and GLY (the active component of Guide drug) on the Wnt signaling pathway was explored systematically. It was a promising breakthrough for elucidating the scientific connotation of the compatibility of TCM formulae and provide a valuable and practicable methodology for clarifying the mechanisms of TCM.

Sustainable Antibacterial Surgical Suture Using a Facile Scalable Silk-Fibroin-Based Berberine Loading System.

Medical sutures with sustainable antibacterial properties can effectively inhibit pathogens, thus avoiding the occurrence of surgical site infection and reducing the recurrence of patients resulting in postoperative death. This paper describes a facile scalable antibacterial surgical suture with sustainable antibacterial function and fair mechanical and biocompatible properties using a simple, efficient, and eco-friendly method. Silk filaments were braided into a core-shell structure using a braiding machine, and then silk fibroin (SF) films loaded with different percentages of berberine (BB) were coated onto the surface of the suture. The drug-loaded sutures performed a slow drug-release profile of more than 7 days. Retention of the knot-pull tensile strength of all groups was above 87% during in vitro degradation within 42 days. The sutures had no toxicity to the cells' in vitro cytotoxicity. The results of the in vivo biocompatibility test showed mild inflammation and clear signs of supporting angiogenesis in the implantation site of the rats. This work provides a new route for achieving a BB-loaded and high-performance antibacterial suture, which is of great potential in applications for surgical operations.

Transcriptome screening followed by integrated physicochemical and structural analyses for investigating RNA-mediated berberine activity.

Non-coding RNAs are regarded as promising targets for the discovery of innovative drugs due to their abundance in the genome and their involvement in many biological processes. Phytochemicals (PCs) are the primary source of ligand-based drugs due to their broad spectrum of biological activities. Since many PCs are heterocyclic and have chemical groups potentially involved in the interaction with nucleic acids, detailed interaction analysis between PCs and RNA is crucial to explore the effect of PCs on RNA functions. In this study, an integrated approach for investigating interactions between PCs and RNAs were demonstrated to verify the RNA-mediated PCs functions by using berberine (BRB) as a model PC. RNA screening of a transcriptome library followed by sequence refinement found minimal RNA motif consisting of a cytosine bulge with U-A and G-U neighbouring base pairs for interaction with BRB. NMR-based structure determination and physicochemical analyses using chemical analogues of BRB demonstrated the importance of electrostatic and stacking interactions for sequence selective interaction and RNA stabilization. The selective interaction with a relatively small RNA motif based on a chemical structure of a planer heterocyclic highlights the biological activities of various PCs mediated by the interactions with particular functional RNAs. In addition, the systematic and quantitative investigations demonstrated in this study could be useful for the development of therapeutic chemicals targeting functional RNAs, based on the PCs, in the future.

Effects of berberine on cholinesterases and monoamine oxidase activities, and antioxidant status in the brain of streptozotocin (STZ)-induced diabetic rats.

Several studies had been conducted to examine the link between diabetes and diabetes encephalopathy. This study was conducted to examine the potency of berberine (BER) on the restoration of impaired neurochemicals in the brain of streptozotocin (STZ)-induced diabetic Wistar rats. Fifty-six (56) adult rats weighing between 200 and 230g were randomly divided into seven groups (n=8) as follows; Group I is normal control; Groups II and III were normal rats treated with 50 and 100mg/kg respectively; Group IV-VII were STZ-induced rats, but Groups V-VII were treated with acarbose (25mg/kg), 50 and 100mg/kg of BER, respectively. The result of the study showed that untreated STZ-induced diabetic rats have increased acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO) activities, and malonylaldehyde (MDA) level, with concomitant decrease of superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, and glutathione (GSH) level. However, daily treatment with 50 and 100mg/kg BER and ACA significantly reversed these effects. The findings of this study clearly indicated that BER possesses neuro-protective and antioxidative potentials and normalize neurochemical impairment distort by diabetes.

Development of Topical Herbal Gel of Berberine Hydrochloride for the Treatment of Psoriasis

Development of Topical Herbal Gel of Berberine Hydrochloride for the Treatment of Psoriasis

Irinotecan and berberine co-delivery liposomes showed improved efficacy and reduced intestinal toxicity compared with Onivyde for pancreatic cancer.

Onivyde is the first irinotecan (IRI) nanoliposome that could improve pharmacokinetics and tumor biodistribution of irinotecan. Although FDA approves Onivyde for the treatment of pancreatic cancer patients who are not effective for GEM, the gastrointestinal toxicity caused by Onivyde is still a problem to be solved in clinical application. Berberine (BER), an isoquinolone alkaloid extracted from several different plants, has been reported to exhibit beneficial effect in alleviating intestinal mucositis and generating synergistic anticancer effect in combination with cytotoxic drugs. However, its therapeutic effect is affected by the different pharmacokinetic behavior of two drugs. Therefore, we utilized triethylamine-sucrose octasulfate gradient to construct nanoliposomes for co-delivery of irinotecan and berberine, termed as lipBI. This co-delivery nanoliposomes remained the synergistic ratio in the body and improved tumor distribution of IRI and BER. The lipBI significantly inhibited tumor growth in the BXPC-3 pancreatic cancer model compared with Onivyde (p<0.05) and reduced the gastrointestinal toxicity in mice caused by IRI. Overall, IRI/BER co-loaded liposomes possessed great potential in the treatment of pancreatic cancer.

Retraction: Berberine alleviates amyloid beta-induced injury in Alzheimer’s disease by miR-107/ZNF217

Retraction of ‘Berberine alleviates amyloid beta-induced injury in Alzheimer’s disease by miR-107/ZNF217’ by Jing Wang et al., RSC Adv., 2019, 9, 25232–25239, DOI: 10.1039/C9RA04500G.

Ratiometric Delivery of Mitoxantrone and Berberine Co-encapsulated Liposomes to Improve Antitumor Efficiency and Decrease Cardiac Toxicity.

Combination therapy is one of the most common clinical practices in the treatment of malignancies. Synergistic effects, however, are produced only when optimal ratios of combined drugs were delivered to tumor cells. Thus, carriers co-encapsulating of multiple drugs are widely utilized for coordinated delivery. Herein, co-encapsulated pegylated liposomal formulation of mitoxantrone (MIT) and berberine (BER) at an optimal ratio has been developed (MBL) with high encapsulation efficiency (EE) and drug loading in order to achieve the purpose of ratiometric loading and delivery. MBL can not only extend blood circulation but also enhance tumor accumulation for both MIT and BER. More importantly, MBL can maintain the originally desired drug ratio in tumors within 48h of intravenous injection for synergistic therapy. Compared with the liposomal formulation of MIT-treated group (ML), the progression of tumor growth was inhibited significantly in murine 4T1 breast tumor model after the treatment of MBL, as well as a lower cardiac toxicity. In addition, MBL evidently prolonged the survival of mice with L1210 ascitic tumor model. In summary, such a strategy of co-encapsulated liposomes could improve the clinical applications against multiple cancers.

Simultaneous Determination of Curcumin and Berberine in their Pure Form and from the Combined Extracts of Curcuma Longa and Berberis Aristata

A simple, rapid, accurate, precise, reliable and economical first derivative spectro- photometric method has been proposed for the simultaneous determination of curcumin (CUR) and berberine (BER) in pure form and in combined methanolic extracts of Curcuma longa and Berberis aristata without any prior separation or purification step. The developed methods show best results in terms of linearity, accuracy, precision, limit of detection (LOD) and limit of quan- tification (LOQ) for standard laboratory mixtures of pure compounds and methanolic extracts of the drugs. The linearity range for curcumin (CUR) and berberine (BER) were found to be 2 to 8 µg mL -1 and 6 to 12 µg mL -1 respectively. The values of LOD were 0.039 µg mL -1 and 0.025 µg mL -1 and the values of LOQ were found to be 0.13 µg mL -1 and 0.08345 µg mL -1 for curcumin (CUR) and berberine (BER) respectively. By this method, C. longa and B. aristata showed 4% w/w curcumin and 2.8% w/w berberine respectively in combined methanolic extracts of the two herbal drugs. The method was validated as per ICH guidelines.

A review on pain-relieving activity of berberine.

As isoquinoline alkaloid naturally occurs in Coptis and Berberis species, berberine (BER) has shown anti-oxidant, anti-tumour, anti-bacterial and hepatoprotective activities and beneficial effects against digestive, cardiovascular and neurological conditions. Also, BER antiinflammatory, pain-relieving and anti-cholinesterase activities were widely studied. The present overview discusses the analgesic effects of BER. Based on the literature, BER exerted pain-relieving activity against diabetic and chemotherapy-induced neuropathy, and sciatic nerve injury-induced pain via down-regulation of transient receptor potential vanilloid 1, suppression of NF-κB and modulation of μ and δ opioid receptors. Besides, BER could repress inflammatory markers tumour necrosis factor-α, interleukin-6 and IL-1β, as well as prostaglandin E2, inducible nitric oxide synthase and cyclooxygenase-2. The modulatory effects of BER on dopamine and N-methyl d-aspartate systems were also noted. Moreover, BER could induce Nrf2 expression but inhibits p38-MAPK and STAT3 phosphorylation. Noteworthy, anti-cholinesterase activity, which may potentially contribute to BER analgesic properties, warrants particular attention.