Novel wine in an old bottle: Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases.

Atherosclerotic cardiovascular disease (ASCVD) frequently results in sudden death and poses a serious threat to public health worldwide. The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets. Therefore, the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention. Andrographolide (AG) is a diterpenoid lactone compound extracted from Andrographis paniculata. In addition to its use in conditions such as sore throat, AG can be used to prevent and treat ASCVD. It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity, diabetes, hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis (AS) including lipid accumulation, inflammation, oxidative stress and cellular abnormalities by regulating various targets and pathways. However, the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated, which may hinder its clinical development and application. Therefore, this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD. The findings support the use of the old pharmacological compound ('old bottle') as a novel drug ('novel wine') for the prevention and treatment of ASCVD. Additionally, this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG, aiming to provide more information regarding the clinical application and further research and development of AG.

A Novel Drug Delivery System: Hyodeoxycholic Acid-Modified Metformin Liposomes for Type 2 Diabetes Treatment.

Metformin is a first-line drug for the clinical treatment of type 2 diabetes; however, it always leads to gastrointestinal tolerance, low bioavailability, short half-life, etc. Liposome acts as an excellent delivery system that could reduce drug side effects and promote bioavailability. Hyodeoxycholic acid, a cholesterol-like structure, can regulate glucose homeostasis and reduce the blood glucose levels. As an anti-diabetic active ingredient, hyodeoxycholic acid modifies liposomes to make it overcome the disadvantages of metformin as well as enhance the hypoglycemic effect. By adapting the thin-film dispersion method, three types of liposomes with different proportions of hyodeoxycholic acid and metformin were prepared (HDCA:ME-(0.5:1)-Lips, HDCA:ME-(1:1)-Lips, and HDCA:ME-(2:1)-Lips). Further, the liposomes were characterized, and the anti-type 2 diabetes activity of liposomes was evaluated. The results from this study indicated that three types of liposomes exhibited different characteristics-Excessive hyodeoxycholic acid decreased encapsulation efficiency and drug loading. In the in vivo experiments, liposomes could reduce the fasting blood glucose levels, improve glucose tolerance, regulate oxidative stress markers and protect liver tissue in type 2 diabetic mice. These results indicated that HDCA:ME-(1:1)-Lips was the most effective among the three types of liposomes prepared and showed better effects than metformin. Hyodeoxycholic acid can enhance the hypoglycemic effect of metformin and play a suitable role as an excipient in the liposome.

A "Trojan Horse" Strategy: The Preparation of Bile Acid-Modifying Irinotecan Hydrochloride Nanoliposomes for Liver-Targeted Anticancer Drug Delivery System Study.

The bile acid transport system is a natural physiological cycling process between the liver and the small intestine, occurring approximately 6-15 times during the day. There are various bile acid transporter proteins on hepatocytes that specifically recognize bile acids for transport. Therefore, in this paper, a novel liposome, cholic acid-modified irinotecan hydrochloride liposomes (named CA-CPT-11-Lip), was prepared based on the "Trojan horse" strategy. The liposomes preparation process was optimized, and some important quality indicators were investigated. The distribution of irinotecan hydrochloride in mice was then analyzed by high-performance liquid chromatography (HPLC), and the toxicity of liposomes to hepatocellular carcinoma cells (HepG-2) was evaluated in vitro. As a result, CA-CPT-11-Lip was successfully prepared. It was spherical with a particle size of 154.16 ± 4.92 nm, and the drug loading and encapsulation efficiency were 3.72 ± 0.04% and 82.04 ± 1.38%, respectively. Compared with the conventional liposomes (without cholic acid modification, named CPT-11-Lip), CA-CPT-11-Lip had a smaller particle size and higher encapsulation efficiency, and the drug accumulation in the liver was more efficient, enhancing the anti-hepatocellular carcinoma activity of irinotecan hydrochloride. The novel nanoliposome modified by cholic acid may help to expand the application of irinotecan hydrochloride in the treatment of hepatocellular carcinoma and construct the drug delivery system mode of drug liver targeting.

[Therapeutic Effect of Autologous Platelet-rich Gel in the Treatment of Chronic Skin Ulcer with Tophus].

OBJECTIVE: To evaluate the clinical effectiveness and safety of autologous platelet-rich gel (APG) in the treatment of chronic skin ulcer with tophus. METHODS: Four patients of chronic skin ulcer with tophus received routine debridement to remove necrotic tissue and erasion tophus as far as possible,and then received the treatment of APG. RESULTS: All of the patients had their wounds healed after the treatment of APG (one wound was treated twice). The wounds were healed between 8 to 22 d, average (13. 7±6. 8) d, while there were no adverse effects observed. CONCLUSION: Topical therapy with APG may be considered as an effective and safe adjuvant method for the treamtment of chronic skin ulcer with tophus.

[Study on pharmacokinetics and in vitro/in vivo correlation of menthol in Zhike Chuanbei Pipa dropping pills in rats].

To determine the concentration of menthol in rat plasma by GC. Rats were administered with single dose of Zhike Chuanbei Pipa dropping pills (ZCPDP) and different doses of menthol herbs. DAS 3. 1.6 software was used to calculate pharmacokinetic parameters, and the accumulative absorption percentage of menthol was calculated by Loo-Riegelman method. The linear regression analysis was made in vitro/in vivo accumulative absorption percentages to detect the in vitro/in vivo correlation. The results of the study showed that the pharmacokinetics behavior of menthol in ZCPDP was in conformity with two-compartment model characteristics. The main parameters were: tmax was 10 min, t1/2beta was (183. 93 52. 75) min, CL/F was (0. 426 +/- 0. 194) L . min-1 . kg-1, all of which were no difference between ZCPDP and menthol herbs with the same dosage. There were significant differences in tmax, t1/2beta, CL/F between menthol herbs with different dosages (P <0. 05) , with indirect proportion between AUC0-infinity and dosage. The regression equation of ZCPDP's accumulative absorption percentage and accumulative release percentage was Fa = 1. 160 3Q - 19. 968, r = 0. 981 3. These results suggested that the pharmacokinetics behavior was similar between ZCPDP and menthol herbs with the same dosage in rats, with good in vitro/in vivo correlation. There were significant differences in pharmacokinetics of menthol in the range of 19.2-570 mg . kg-1.

[In vitro studies on the growth and proliferation characteristics of rat bone mesenchymal stem cells].

OBJECTIVE: This study was to investigate the growth and proliferation characteristics of rat bone mesenchymal stem cells (BMSCs) isolated by the method of whole bone marrow culture and to explore the effect of cell inoculation density and incubation period on cell proliferation, with an aim to provide multipotential seed cells for preventing from degenerative disease. METHODS: Bone mesenchymal stem cells were isolated by the method of whole bone marrow culture and then cultured in vitro. The cell morphologic features were observed by inverted microscope. The cell surface antigens were identified by flow cytometry. The effect of cell inoculation density and culture period on cell growth and proliferation was explored by analyzing the characteristics of a ten-day cell growth curve in 96-well plates. RESULTS: Flow cytometry results showed the detection rates for CD29, CD34 and CD45 were 97.68% (7607/7788), 7.93% (661/8340) and 2.76% (215/7788) respectively, which was consistent with the expression characteristics of BMSCs surface antigens. BMSCs became uniform after three cell passages, existing in a typical shape of whirlpool or radial colony. The senescent cells started to appear at 7(th) passage, and more senescent cells were found at 10(th) passage. The growth curve for moderate inoculation density was typically S-shaped. Lag phase was found during the first two days, and logarithm growth phase was in the following three days. Plateau phase started from the 6(th) day and cell numbers decreased slightly from the 8(th) day. CONCLUSION: The whole bone marrow culture is an effective way to obtain BMSCs. A moderate inoculation density was more advantageous to cell proliferation, by which more seed cells could be obtained.