Lizhen Wang

Bio: Lizhen Wang is an academic researcher from Qilu University of Technology. The author has contributed to research in topics: Berberine & Medicine. The author has an hindex of 9, co-authored 41 publications receiving 191 citations.

Recent progress on the organic and metal complex-based fluorescent probes for monitoring nitric oxide in living biological systems.

Abstract: Nitric oxide (NO) is an important gaseous signaling molecule related to various human diseases. To investigate the biological functions of NO, many strategies have been developed for real-time monitoring the NO levels in biological systems. Among these strategies, fluorescent probes are considered to be one of the most efficient and applicable methods owing to their excellent sensitivity and selectivity, high spatiotemporal resolution, noninvasiveness, and experimental convenience. Therefore, great efforts have been paid to the design, synthesis, and fluorescence investigation of novel NO fluorescent probes in the past several years. However, few of them exhibit practical applications owing to the low concentration, short half-life, and rapid diffusion characteristics of NO in biological systems. Rational design of NO fluorescent probes with excellent selectivity and sensitivity, low cytotoxicity, long-lived fluorescent emission, and low background interference is still a challenge for scientists all over the word. To provide spatial-temporal information, this article focuses on the progress made in the organic and metal complex-based NO fluorescent probes during the past five years. The key structural elements and sensing mechanisms of NO fluorescent probes are discussed. Some novel ratiometric, luminescence, and photoacoustic probes with low background interference and deep tissue penetrating ability are mentioned. All these probes have been used for imaging exogenous and endogenous NO in cells and animal models. More importantly, this article also describes the development of multi-functional NO fluorescent probes, such as organelle targeting probes, dual-analysis probes, and probe-drug conjugates, which will inspire the design of various functional fluorescent probes.

Anti-Inflammation Associated Protective Mechanism of Berberine and its Derivatives on Attenuating Pentylenetetrazole-Induced Seizures in Zebrafish.

Abstract: Epileptic seizures are characterized by synchronized discharges of neurons, leading to the activation of inflammatory responses that in turn contributes to seizure progression. Berberine (BBR), a bioactive constituent extracted from berberis, has been known to relieve seizures in rodent models. In this study, we synthesized two derivatives of berberine (BBR-D1 and BBR-D2) to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. We found a structure-activity relationship between hydrophilic/hydrophobic composition of the derivatives and their anticonvulsant activity. We also investigated the underlying mechanism related to their anti-inflammatory effect during seizures. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives. Our results suggest that BBR and its derivatives attenuate PTZ-induced seizures and modulate anti-inflammatory effect to potentially protect zebrafish from the occurrence of further seizures. From the tested compounds, BBR-D1 (the hydrophilic berberrubine) showed the strongest seizure reducing effect. Graphical Abstract Two derivatives of berberine (BBR-D1 and BBR-D2) were synthesized to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives.

Novel carbohydrate modified berberine derivatives: synthesis and in vitro anti-diabetic investigation.

Abstract: Berberine is a bioactive alkaloid used in Chinese medicine and has numerous positive effects on biological systems. This paper describes the facile and highly efficient synthesis of some carbohydrate modified berberine derivatives, and conjugation of the carbohydrate moiety with berberine was finished by “click” chemistry. The cytotoxicity and anti-diabetic measurements of all berberine derivatives were accomplished on HepG2 cell lines, and the results indicated that most of the derivatives exhibit higher anti-diabetic activity than berberine. The mannose modified berberine derivative has significantly lower cytotoxicity than berberine, and the induced IC50 value of this derivative is nearly 1.5 times that of berberine. Furthermore, this mannose modified berberine derivative exhibits high anti-diabetic activity at both high and low drug concentrations, thereby indicating its potential application for the development of novel anti-diabetic drugs.

Metabolomics for Biomarker Discovery in Fermented Black Garlic and Potential Bioprotective Responses against Cardiovascular Diseases

Abstract: Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.

Synthesis of disaccharide modified berberine derivatives and their anti-diabetic investigation in zebrafish using a fluorescence-based technology.

Abstract: Berberine is a naturally occurring isoquinoline alkaloid and has been used as an important functional food additive in China due to its various pharmacological activities. Berberine exhibits great potential for developing anti-diabetic agents against type 2 diabetes mellitus (T2DM), as it can reduce the blood glucose level in many animal models. However, the low anti-diabetic activity and poor bioavailability of berberine (below 5%) by oral administration significantly limit its practical applications. To solve these problems, this article focuses on the structural modification of berberine using some disaccharide groups, because the carbohydrate moiety has been proved to improve the bioavailability and enhance the receptor-binding affinity of drugs. Anti-diabetic investigation of the synthesized compounds was performed in a zebrafish model using a fluorescently labelled glucose analog 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a glucose tracker. The results indicated that the modification of berberine with carbohydrate groups could give derivatives with improved anti-diabetic activity, in particular the diglucose modified berberine derivative 1 which could dramatically promote the uptake of 2-NBDG in both zebrafish larvae and their eyes even at very low concentrations. Furthermore, the fluorescence-based anti-diabetic investigation method in zebrafish shows great potential for anti-diabetic drug screening.

CuAAC-ensembled 1,2,3-triazole-linked isosteres as pharmacophores in drug discovery: review

Abstract: The review lays emphasis on the significance of 1,2,3-triazoles synthesized via CuAAC reaction having potential to act as anti-microbial, anti-cancer, anti-viral, anti-inflammatory, anti-tuberculosis, anti-diabetic, and anti-Alzheimer drugs. The importance of click chemistry is due to its ‘quicker’ methodology that has the capability to create complex and efficient drugs with high yield and purity from simple and cheap starting materials. The activity of different triazolyl compounds was compiled considering MIC, IC50, and EC50 values against different species of microbes. In addition to this, the anti-oxidant property of triazolyl compounds have also been reviewed and discussed.

The Anti-Cancer Mechanisms of Berberine: A Review.

Abstract: Berberine (BBR) has been extensively studied in vivo and vitro experiments. BBR inhibits cell proliferation by regulating cell cycle and cell autophagy, and promoting cell apoptosis. BBR also inhibits cell invasion and metastasis by suppressing EMT and down-regulating the expression of metastasis-related proteins and signaling pathways. In addition, BBR inhibits cell proliferation by interacting with microRNAs and suppressing telomerase activity. BBR exerts its anti-inflammation and antioxidant properties, and also regulates tumor microenvironment. This review emphasized that BBR as a potential anti-inflammation and antioxidant agent, also as an effective immunomodulator, is expected to be widely used in clinic for cancer therapy.

Recent progress in chemosensors based on pyrazole derivatives

Abstract: Colorimetric and fluorescent probes based on small organic molecules have become important tools in modern biology because they provide dynamic information concerning the localization and quantity of the molecules and ions of interest without the need for genetic engineering of the sample. In the past five years, these probes for ions and molecules have attracted great attention because of their biological, environmental and industrial significance combined with the simplicity and high sensitivity of absorption and fluorescence techniques. Moreover, pyrazole derivatives display a number of remarkable photophysical properties and wide synthetic versatility superior to those of other broadly used scaffolds. This review provides an overview of the recent (2016–2020) findings on chemosensors containing pyrazole derivatives (pyrazoles, pyrazolines and fused pyrazoles). The discussion focuses on the design and physicochemical properties of chemosensors in order to realize their full potential for practical applications in environmental and biological monitoring (sensing of metal ions, anions, explosives, and biomolecules). We also present our conclusions and outlook for the future.

Phytopharmacology and Clinical Updates of Berberis Species Against Diabetes and Other Metabolic Diseases.

Abstract: The incidences of diabetic mellitus and other metabolic diseases such as hypertension and hyperlipidemia are increasing worldwide; however, the current treatment is not able to control the rapidly increasing trend in diabetes mortality and morbidity. Studies related to the effectiveness of extracts and pure compounds obtained from plants have shown promising responses in preclinical and clinical studies related to these metabolic diseases. Plants belonging to the genus Berberis (Family: Berberidaceae) are widely distributed with nearly 550 species worldwide. Extracts and compounds obtained from Berberis species, especially Berberine alkaloid, showed effectiveness in the management of diabetes and other metabolic diseases. Various pharmacological experiments have been performed to evaluate the effects of Berberis extracts, berberine, and its natural and chemically synthesized derivatives against various cell and animal disease models with promising results. Various clinical trials conducted so far also showed preventive effects of Berberis extracts and berberine against metabolic diseases. The present review focuses on i) research updates on traditional uses, ii) phytopharmacology and clinical studies on Berberis species, and iii) active metabolites in the prevention and treatment of diabetes and other metabolic diseases with a detailed mechanism of action. Furthermore, the review critically analyzes current research gaps in the therapeutic use of Berberis species and berberine and provides future recommendations.