Scutellariabarbata D. Don (S. barbata), a medicinal herb commonly used in traditional Chinese and Korean medicine, consists of bioactive neoclerodanes and flavonoids. However, its anti-hyperglycemic activity has not been reported. In this work, we used bioassay-guided fractionation to find effective anti-hyperglycemic fractions of S. barbata. The chemical components of these fractions were also determined structurally; they are scutellarin (1), luteolin (2), naringenin (3), tricin (4), baicalein (5), baicalin (6), apigenin (7), and wogonin (8). The most potent fraction SB6 consisting of flavonoids 5, 6, 7, and 8 showed 89% inhibition of alpha-glucosidase in the in vitro experiment. In further in vivo experiments on streptozotocin (STZ)-induced diabetic mice, SB6 exhibited significant anti-hyperglycemic activity comparable to metformin after 28 days of treatment. This fraction, however, did not show efficiency in reducing the weight gain of the treated mice.

A capsaicin patch was formulated by optimizing the adhesion, the release behavior of the patch, and the pharmacological effect. The aims of study were to 1) apply the design of experiments approach for investigating the simultaneous effect of Viscomate (partially neutralized polyacrylate)-based adhesive, glycerin plasticizing excipient and permeation enhancers on patch adhesion, and the permeation rate of model drug (capsaicin) and then 2) compare the optimal formulation with the reference product (Wellpatch (R), Metholatum, U.S.A.) in terms of pharmacological effect. The topical patch was prepared by casting the drug-loaded adhesive hydrogel on the backing layer. The adhesive ability of patches was determined by testing a 90 degrees peel rig on a texture analyzer, and the permeation rate of capsaicin (CAP) through mouse skin was evaluated using Franz diffusion cells. The effects of these critical factors on patch adhesion, CAP flux, and permeation enhancer interaction with the stratum corneum were analyzed using ANOVA and ATR-FTIR/skin hydration tests, respectively. Accordingly, Viscomate (adhesion excipient) and glycerin (plasticizing excipient) had a significant impact on patch adhesion (p < 0.05). Meanwhile, N-methyl pyrrolidone, the permeation enhancer, had a better permeation rate and higher hydration level of the stratum corneum than did Transcutol. The partially neutralized polyacrylate-based optimal formu-lation had a higher permeation rate of CAP, equal adhesion and comparable anti-inflammatory effects to those of the reference product which was also in agreement with the analysis of anatomical images of tissue structure and inflammatory cells. This study successfully integrated DoE method, release behavior and pharmacological research to develop a stable and highly effective topical product containing capsaicin.

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14647.].

Objective Heliciopsis terminalis (Kurz.) Sleum (family Proteaceae) is distributed in India, Mianma, Thailand, Cambodia, Vietnam, and China. In Vietnamese traditional medicine, it is used as an antidote for detoxifying the liver and detoxifying alcohol, a contraceptive, and to treat infections. The purpose of this study is to determine the chemical constituents of the plant, as well as their in vitro hepatoprotective and antioxidant activities. Methods The dried powdered sample was ultrasonically extracted with MeOH, and the extract was fractionated by various chromatographic methods, including high-performance liquid chromatography. The structures of the isolated compounds were identified by NMR, high-resolution electrospray ionization mass spectrometry, and CD spectral analysis, and then screened for their in vitro hepatoprotective and antioxidant activities. Results One new phenolic glycoside, named helitermioside (1), and eight known compounds (2-9) were isolated from the trunk and branches of H terminalis. All of the isolates were reported from H terminalis for the first time. Compound 6 showed antioxidant activity in thiobarbituric acid reactive substances (TBARS) lipid peroxidation inhibition assays, with an IC50 value of 61.16 ± 1.17 µg/mL, compared to that of Trolox (positive control), IC50 = 7.06 ± 0.11 µg/mL. At a concentration of 100 µg/mL, none of the isolates exhibited hepatocellular protective activity. Conclusion Nine phenolic compounds (1–9) were recorded from H terminalis. Of these, compound 1 was new. Compound 6 exhibited moderate antioxidant activity in TBARS lipid peroxidation inhibition assays, but none of the compounds exhibited hepatocellular protective activity against CCl4-induced toxicity.

The ATR-FTIR quantitation of azithromycin in three products of commercial tablets was carried out on product specific quantitative regression models using powdered paracetamol as matrix modifier to overcome the variation of spectral response and influence of sample matrix. For each product, a PLS quantitative regression model was established using training infrared spectra obtained from reference mixtures (reference powders with known mass content (%, w/w) of azithromycin mixed homogenously with paracetamol to have mass percentage of azithromycin over total mass of azithromycin and paracetamol (PA) from 30% to 70%). The spectral data were collected in wavenumber range depending on commercial product within the wavenumber zone from 1300 cm-1 to 1750 cm-1 to build quantitative regression models. To quantify azithromycin in any commercial batch of the same product, the homogenized sample powder was mixed with paracetamol to have mixtures with PA value about 50% to record infrared spectrum. The actual amount of azithromycin would then be calculated from spectral response of unknown sample and the pre-established quantitative regression model. Each quantitative regression model was validated according to the current requirements of ICH guideline Q2R1 and those of AOAC International in term of specificity, accuracy, precision, long-term robustness and reliability. The validation results proved that the quantitative regression models were accurate, precise, reliable and robust, able to provide quantitative results of azithromycin in tablets equivalent to those provided by official HPLC method of USP44.

According to the traditional know-how, the Northern wild pineapple (Pandanus tonkinensis) has been used efficiently as a major component of oriental remedies for liver protection. Based on the experimentally found chemical composition of Pandanus tonkinensis and their obtained biological activities in terms of the hepatoprotection purpose, two structure-elucidated compounds pinoresinol 4-O-beta-D-glucopyranoside and vladinol F were selected as potential markers for this medical plant. This paper is aiming to present the validation of proposed HPLC method for simultaneous quantification of the both pinoresinol 4-O-beta-D-glucopyranoside and vladinol F in the fruits of Pandanus tonkinensis with the following conditions: using RP-C18 (250 mm × 4.6 mm; 5 μm) column, detection wavelength measured at 228 nm, the mobile phases consisting of acetonitrile and 0.1% acetic acid in gradient mode with a flow rate of 1mL/min and injection volume was 10 mL. Method validation showed a high specificity, linear calibration ranging from 25.5 to 76.4 mg/ml (r= 0.9991) and from 26.0 to 77.9 mg/ml (r= 0.9987) for two markers, respectively. Besides, a good repeatability and intermediate precisions (RSD < 2%), a reliable accuracy (recovery efficiency between 99.4 and 101.5%, RSD < 1.73%) as well as the obtained limits of quantification in values of 2.55 m/g and 2.60 mg/g for the two mentioned markers were received. Using the above validated method, the content of two markers - pinoresinol 4-O-beta-D-glucopyranoside and vladinol F in Pandanus tonkinensis fruits collected from different locations (Thanh Hoa, Hoa Binh, Thai Nguyen) had been determined falling in the range of 0.0250 - 0.0435 mg/g and 0.0243 - 0.0371 mg/g, respectively. Keywords: pinoresinol 4-O-beta-D-glucopyranoside, vladinol F, markers, Pandanus tonkinensis, HPLC

Heliciopsis lobata (Merr.) Sleumer is a popular herbal material in the North-West territories of Vietnam. The wood of this plant is still used for the treatment of some liver diseases, although there is no scientific evidence for evaluating these activities and the safety of this herbal material. Our study focused on accessing acute toxicity and hepatoprotective activity of water extract from the wood of Heliciopsis lobata. Among experimental groups of mice induced by high dosage of paracetamol, mice were treated with extract at dosages of 0.56 g/kg, 1.15 g/kg and 2.30 g/kg could be against liver damage with different levels. Water extract at dosages of 0.56 g/kg and 1.15 g/kg could maintain the original situation of livers; significantly reduced the increase of ALT and AST enzymes at levels of about 80% and 87% respectively; significantly reduced 70% the increase of AST, and against most of the peroxidation process in liver tissue. A dosage of 2.30 g/kg expressed lower hepatoprotective activities in comparison with the former dosages and which may increase liver toxicity when used with high dosages of paracetamol. The highest experimental dosage at 32.60 g/kg did not show acute toxicity by independent oral administration. It could be concluded that water extract of the wood of Heliciopsis lobata exposed hepatoprotective ability with dosage from 0.56 g/kg to 1.15 g/kg, equivalent to dosages from 60 g to 120 g for humans per day. Keywords: Hepatoprotective, ALT, AST, TBARs, Heliciopsis lobata, acute toxicity.

A simple, easy-to-implement, and green infrared spectroscopic method was developed and validated for the quantitative determination of sildenafil citrate in tablets of unknown manufacturing formula. Homogenized tablet powder with known mass content (%, m/m) of sildenafil citrate was mixed with paracetamol to form standard mixtures with different percentages of sildenafil citrate on the total quantity of sildenafil citrate and paracetamol (designated as R). Unknown tablet samples were finely ground and mixed with paracetamol to form test mixtures having R values about 50%. Infrared spectra of standard mixtures, measured in attenuated total reflectance mode, in the wavenumber zone from 1800 cm−1 to 1300 cm−1 were selected and processed by partial least square regression to form the calibration model for quantitation of sildenafil citrate in unknown samples. Spectral responses of test mixtures and the calibration model were used to determine the exact mass content (%, m/m) of sildenafil citrate in the powder of unknown tablet samples. The method was fully validated in terms of linearity, precision, and accuracy according to the requirements of current guidelines and was proved as reliable and suitable for the intended application.

A new macrocyclic glycoside named helilobatoside A (1) and 5 known phenyl glycosides as 3,5-dimethoxy-4-hydroxyphenyl-1- O-β-d-glucopyranoside (2), tachioside (3), isotachioside (4), 1-(4-hydroxy-3-methoxyphenyl)-1-propanone-3- O-β-d-glucopyranoside (5), and 1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-3- O-β-d-glucopyranoside (6), were isolated from the wood of Heliciopsis lobata (Merr.) Sleumer. Their chemical structures were elucidated using a combination of high-resolution electrospray ionization mass spectrometry, 1-dimensional (1D) and 2D nuclear magnetic resonance (NMR) spectral data as well as by comparison with data in the previous literature. This is the first time the 13C NMR data of compounds 5 and 6 were reported and also were assigned by heteronuclear single quantum correlation and heteronuclear multiple bond correlation spectra. Compounds 2-6 were first isolated from Heliciopsis genus. The isolated compounds were evaluated for their antioxidant and hepatoprotective activities in vitro. Compound 2 showed potential as an antioxidant in a 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay (half-maximal inhibitory concentration [IC50] = 6.07 ± 0.17 µg/mL) and in thio-barbituric acid reactive substances assay (IC50 = 89.55 ± 8.26 µg/mL). This compound could also reduce the toxic effects of carbon tetrachloride on HepG2 survival and significantly protect the viability of cells up to 52.25 ± 4.36% at the 100 µg/mL treatment ( P < 0.05). Thus, with obtained results, the hepatoprotective activity of compound 2 could be related to radical scavenging and limited the lipid peroxidative activities.

A bisresorcinol, (8 ' Z)-3,5-dihydroxy-1-[16 '-(3 ",5 "-dihydroxyphenyl)-8 '-hexadecen-1 '-yl]benzene (I), was isolated as an abundant constituent from the Vietnamese medicinal plant Heliciopsis terminalis (Kurz) Sleumer (Proteaceae). The antioxidant, hepatoprotective, and anti-inflammatory activities of compound I were tested in correlation with the use of H. terminalis as a hepatoprotective drug by ethnic people in Vietnam. Bisresorcinol I showed weak scavenging activity against DPPH radical at an EC50 value of 156.9 mg/mL. At a concentration of 100 mg/mL, compound I inhibited 19,78% of MDAproduction as one of the biomarkers for lipid peroxidation. Bisresorcinol I protected HepG2 cells against harmful CCl4. The hepatoprotective ability was observed at a concentration of 100 mg/mL with up to 44.42% cells alive, which was significantly higher than that in the control treated with CCl4 (29.93 %). The NO scavenging activity of I was determined in RAW 264.7 cells with an IC50 value of 71.15 mg/mL. Bisresorcinol I exhibited its anti-inflammatory activity through modulation of proinflammatory cytokines IL-6 and TNF-alpha as well as anti-inflammatory IL-10 in RAW264.7 cells.

This paper aimed at developing a simple and fast approach using chemometrics processing for direct assay of acyclovir in tablets by NIR (near infrared) spectroscopy in diffuse reflectance mode.In making trials with 5 different tablet matrices, the experimental results showed that regardless the matrix variation, it was always possible to construct a quantitative model with suitable linear range, accuracy and precision for direct assay of acyclovir in tablet from NIR spectra.Therefore, the approach used in this study was suitable for on-site fast assay of APIs in tablets during manufacturing process or in post-marketing surveillance of drug quality.