Search

Diabetes is a common chronic metabolic disease. Different types of drugs play important roles in controlling diabetes and its complications, but there are some limitations. The glucose-responsive drug delivery system is a novel technology with potential in diabetes treatment. It could automatically release drugs in response to changes in glucose levels in the body to maintain blood glucose within a normal range. The emergence of a glucose-sensitive drug delivery system provides a more intelligent and precise way to treat diabetes. The review is carried out according to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines This review focuses on the recent advances in the drugs and different systems of glucose-sensitive drug delivery, including glucose oxidase, phenylboronic acid, Concanavalin A, and other glucose-reactive systems. Furthermore, the glucose-responsive drug delivery system combined with the application applied in hydrogels, microneedles, and nanoparticles is also explored and summarized. The new platforms to sustain the release of anti-diabetic drugs could be desirable for patients. It could lead to increased adherence and glycemic outcomes for the detection and treatment of diabetes. Furthermore, given the limitations of glucose-responsive drug delivery systems, solutions and perspectives are proposed to help the understanding and application of these systems. This review will be helpful for drug discovery and treatment of diabetes from a new perspective.

Objective: A phenylbutenoid extract (PE) was obtained from Zingiber cassumunar rhizomes. Phenylbutenoids; namely DMPBD, compound D, and compound D acetate, have been identified as major anti-inflammatory and analgesic constituents. This present study aimed to formulate a gel containing PE that could be used as an alternative ultrasound gel for acute or chronic inflammatory treatment. Material and Methods: Gel formulations containing 0.5, 1, and 2% w/w PE were prepared using Carbopol 934 and hydroxyethylcellulose (HEC 4,000) as gelling agents. The contents of phenylbutenoids were quantified by a high-performance liquid chromatography (HPLC). PE gels were studied on physicochemical properties and accelerated stability tests. The PE gels, F2 and F5, were used to evaluate the release of phenylbutenoids using a modified Franz diffusion cell. In the skin permeation study, the 2% PE gels were applied either with or without a 0.8 W/cm2 intensity ultrasound for 2, 5, and 10 min. Results: Based on physicochemical properties and accelerated stability tests, F2 and F5 formulations showed good stability. The release kinetics of 0.5% and 1% and 2% w/w PE of both formulations were best fit to Higuchi’s model and zero-order model, respectively. In the skin permeation study, PE gel combined with ultrasound application for 2 min exhibited higher phenylbutenoids in the skin and also a shorter lag time than PE gel application alone. Conclusion: The gel containing 2% w/w phenylbutenoid extract was suggested as an alternative ultrasound gel containing an anti-inflammatory agent for the treatment of musculoskeletal disorders in phonophoresis.

Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of −7.5 and −6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in vitro assay on α-glucosidase revealed that THC and CBD exhibited good inhibitory activity, with the IC50 values of 3.0 ± 0.37 and 5.5 ± 0.28 μg/ml, respectively. These were better than the standard drug, acarbose (IC50 of 488.6 ± 10.23 μg/ml). Furthermore, two standardized cannabinoid extracts, SCE-I (C. sativa leaf extract) and SCE-II (C. sativa inflorescence extract) exhibited stronger inhibitory activity than THC and CBD, with the IC50 values of 1.2 ± 0.62 and 0.16 ± 0.01 μg/ml, respectively. The present study provides the first evidence that the standardized cannabinoid extracts containing THC and CBD have greater potential than CBD and THC in application as an α-glucosidase inhibitor.

Abstract The simultaneous and sequential dual elicitation effect on plumbagin production in Plumbago indica L. root cultures, revealed that combination of chitosan (150 mg L−1) with ʟ-alanine (5 mM) or methyl-β-cyclodextrin (MCD; 2 mM) significantly increased plumbagin production, but in the different treatment manners. The simultaneous treatment using chitosan + ʟ-alanine on a 14-day-old culture enhanced plumbagin production to 14.62 mg g−1 DW, while the sequential additions of MCD to a 12-day-old culture followed by chitosan after 48 h enhanced production of plumbagin to 14.33 mg g−1 DW. The plumbagin productivity from both treatments were up to 1.3- and 8-fold higher than the chitosan treated (10.93 mg g−1 DW) and untreated root cultures (1.76 mg g−1 DW). Moreover, the present studies provided new information on the effect of simultaneous and sequential elicitation on plumbagin-producing P. indica root cultures using chitosan in combinations with MCD or ʟ-alanine.

Objective: To evaluate the immunosuppressive effect on human phagocytes and antibacterial activity of dihydromorin and norartocarpetin isolated from Artocarpus heterophyllus heartwoods. Methods: Dihydromorin and norartocarpetin were isolated from Artocarpus heterophyllus heartwoods. A modified Boyden chamber was used to determine the chemotactic activity of human phagocyte. The respiratory burst was evaluated by chemiluminescence assay. Myeloperoxidase (MPO) activity was quantified using a colorimetric assay. The broth microdilution method was performed to assess their antibacterial activity. Results: Dihydromorin exhibited potent inhibitory effect on the chemotactic activity of polymorphonuclear neutrophils (PMNs) with an IC50 value of 5.03 μg/mL. Dihydromorin also inhibited reactive oxygen species production of whole blood cells, PMNs, and monocytes with IC50 values of 7.88, 7.59 and 7.24 μg/mL, respectively. Interestingly, dihydromorin also strongly inhibited the MPO activity of PMNs with an IC50 value of 5.24 μg/mL, which was lower than indomethacin (24.6 μg/mL). Molecular docking of dihydromorin and crystal structure of MPO showed that dihydromorin had close interaction with key amino acid residues such as Arg239 and Gln91. Antibacterial activity assay showed that only dihydromorin had a strong effect against Streptococcus pyogenes with MIC and MBC values of 15.62 and 31.25 μg/mL, respectively. Conclusions: The results suggest that dihydromorin could be developed as an anti-inflammatory and antibacterial agent.

Rhinacanthus nasutus (R. nasutus) leaf extract was prepared and standardized to obtain rhinacanthins rich extract that contained total rhinacanthin-C (Rn-C) of not less than 70% w/w. Rn-C was also isolated from the standardized R. nasutus leaf extract (SRLE). SRLE was investigated on pain and inflammatory models in parallel with its main naphthoquinone constituent, Rn-C in order to compare their efficacy in experimental animals. The analgesic activities of SRLE and Rn-C were evaluated by the acetic acid-induced writhing test, a hot-plate test and formalin test at doses of 20, 40, and 80 mg/kg. The anti-inflammatory activities were investigated by carrageenan induced paw edema and the cotton pellet induced granuloma in rats at doses of 80, 160, and 320 mg/kg. SRLE and Rn-C inhibited the acetic acid induced writhing in a dose dependent manner; inhibited the early phase of the formalin test at 80 mg/kg and the late phase at 40 and 80 mg/kg. However, none of the tested doses were effective in protecting against the hot plate test. In the animal models of inflammation, SRLE and Rn-C dose dependently inhibited edema formation in the carrageenan induced paw edema and suppressed granuloma formation in the cotton pellet induced granuloma in rats. The effects of SRLE in these tests were similar to those of the Rn-C. This study confirms the analgesic and anti-inflammatory activities of SRLE and Rn-C in animal models as well as demonstrating that they have a similar efficacy.

Garcinia cowa Roxb., locally called "Cha-muang" in Thailand, serves as a culinary ingredient and a key component of Thai traditional medicine. Its phytochemical analysis uncovered a range of secondary metabolites, including xanthones, phloroglucinols, polyprenylated benzophenones, etc., that displayed notable anticancer activities against human cancer cell lines. Among xanthones, jacareubin (1) obtained from the roots and leaves and cowanin (8) isolated from the roots and twigs stand out as noteworthy anticancer compounds. Jacareubin exhibited potent cytotoxic effects against oral (KB), pancreatic (PANC-1), lung (A549), and cervical (HeLa) cells (IC 50 < 10 μM). Similarly, cowanin displayed immense cytotoxic activity against human cancer cell lines, namely lung (H-460) and HeLa cells (IC 50 < 6 μM). Moreover, garcowacinol C (30), a phloroglucinol found in the twigs, displayed cytotoxicity against KB, breast (MCF-7), colon (HeLaS3), colorectal (HT-29), and liver (HepG-2) cells (IC 50 < 10 μM), while chamuangone (50), a benzophenone derivative, isolated from the leaves, showed substantial cytotoxic effects against lung (SBC-3 and A549), leukemia (K562 and K562/ADM), HT-29, MCF-7, and HeLa cells (IC 50 < 8 μM). Furthermore, chamuangone also induced apoptosis in HeLa cells by inhibiting the epidermal growth factor receptor tyrosine kinase (EGFR-TK) and inhibiting metastasis by suppressing HeLa cell migration. Besides, G. cowa has been explored for its antimicrobial, antioxidant, anti-inflammatory, antidiabetic, and gastroprotective properties. Concludingly, this review narrates the traditional uses of G. cowa alongside its phytochemical and biological attributes, with a particular emphasis on its anticancer potential. [Display omitted] • The major phytoconstituents and their biological importance of G. cowa are illustrated. • Chamuangone stands out as the most noteworthy anticancer compound found in G. cowa. • Jacareubin exhibits anti-cancer, along with anti-inflammatory and anti-allergic properties. • Cowanin displays cytotoxicity against lung and cervical cancers. • Garcowacinol C shows potent effects against oral cancer. [ABSTRACT FROM AUTHOR]

Using DPPH radical scavenging assay to investigate the antioxidant activity of crude methanol extracts from the leaves, flowers and pods of Cassia alata L. found that the leaf extract exhibited a stronger antioxidant activity than the extracts from the flowers and pods. On the basis of DPPH radical scavenging assay-guided isolation, the methanol extract of C. alata leaves was separated by silica gel vacuum chromatography and Sephadex LH-20 gel filtration chromatography afford a light yellowish powder (CA1), which was identified as kaempferol. This compound exhibited antioxidant activity (ED50 9.99 μM) that was six times stronger than that of BHT (ED50 57.41 μM) and fifty eight times stronger than that of emodin (ED50 578.87 μM).

Analyses have been carried out on the content of hydroxyanthracene derivatives of the leaves, flowers and pods of Cassia alata, which had been collected at different harvesting times and different leaf-positions. It was found that when the leaves had been harvested in March, June or September, the hydroxyanthracene derivatives were accumulated more in the leaf-positions 1-3 (1.82, 1.25, 1.63 %w/w, respectively) and 4-6 (1.39, 1.58, 1.09 %w/w, respectively). In December (the flowering and fruiting season), hydroxyanthracene derivatives were accumulated more in the flowers (2.21%w/w) and the pods (1.82 %w/w), respectively. The method and temperature of drying markedly affected the hydroxyanthracene derivative content. Drying of the leaves in a hot air oven at 50ºC gave a higher hydroxyanthracene derivative content (1.43 %w/w) than drying in a hot air oven at 80ºC (0.44 %w/w) or drying in the sun (0.95 %w/w). Study on the stability of hydroxyanthracene derivatives in C. alata leaf powder, which was kept in tight container at room temperature, found that the hydroxyanthracene derivative content did not decrease within 9 months.

Bacterial contamination and infection widely affect the food, pharmaceutical and biomedical industries. Additionally, these bacteria developed resistance to synthetic antibiotics causing public health danger, globally. Natural plant extracts (NPE) are suitable alternatives to synthetic antibiotics to tackle antimicrobial resistance problems. Furthermore, a blend or combination of different NPEs exerts a wide spectrum of antimicrobial activity. Therefore, the combined effect of brazilin-rich extract (BRE) and lawsome methyl ether (LME) against infection-causing common bacteria were evaluated. BRE had a lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against most of the Gram-negative bacteria (Salmonella typhi, Salmonella typhimurium and Pseudomonas aeruginosa) while LME was active against most of the Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, and Staphylococcus epidermidis). The combination of BRE and LME at 2:1 and 1:1 concentration significantly reduced the MIC value of each compound as compared to either BRE or LME concentration alone (P < 0.05). Further time-kill kinetics revealed a 3.0–3.5 log reduction in Gram-positive bacteria and a 2.5–3.0 log reduction in Gram-negative bacteria during 120 min of incubation, respectively. Therefore, a combination of BRE and LME was recommended as natural antibacterial to synthetic antibiotics for food and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

A simple and validated HPLC method for quantitative analysis of [6]-gingerol in ginger extracts was established. The optimum HPLC conditions involved a TSK-gel ODS-80 Ts column (5 μm, 4.6 x 250 mm) eluted with acetonitrile and 1% aqueous acetic acid (48:52, v/v), at 30ºC, with a flow rate of 1 mL/min and a quantitative UV detection at 280 nm. A good selectivity, linearity (R2 of 1.0000), accuracy (Recovery of 96.7-103.2%), intraday- and interday-precision (Relative standard deviation (RSD) of less than 2% and 5%, respectively) and sensitivity (LOD and LOD of 0.48 and 0.80 µg/mL, respectively) were obtained. A microwave-assisted extraction was used for preparation of [6]-gingerol enriched ginger extracts. Based on HPLC analysis, the concentrations of [6]-gingerol of the extracts obtained from 20% v/v glycerin in ethanol (0.45 mg/mL) as well as 20% v/v natural deep eutectic solvents (NADES) of sucrose & citric acid in ethanol (0.43 mg/mL) were not significantly different from ethanol (0.42 mg/mL). However, glycerin (20% v/v) or NADES of sucrose & citric acid (20% v/v) might be used as the alternative green solvents for preparation of [6]-gingerol extract that could be directly used for formulation of anti-nausea and vomiting pastilles. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the immunosuppressive effect on human phagocytes and antibacterial activity of dihydromorin and norartocarpetin isolated from Artocarpus heterophyllus heartwoods. Methods: Dihydromorin and norartocarpetin were isolated from Artocarpus heterophyllus heartwoods. A modified Boyden chamber was used to determine the chemotactic activity of human phagocyte. The respiratory burst was evaluated by chemiluminescence assay. Myeloperoxidase (MPO) activity was quantified using a colorimetric assay. The broth microdilution method was performed to assess their antibacterial activity. Results: Dihydromorin exhibited potent inhibitory effect on the chemotactic activity of polymorphonuclear neutrophils (PMNs) with an IC50 value of 5.03 μg/mL. Dihydromorin also inhibited reactive oxygen species production of whole blood cells, PMNs, and monocytes with IC50 values of 7.88, 7.59 and 7.24 μg/mL, respectively. Interestingly, dihydromorin also strongly inhibited the MPO activity of PMNs with an IC50 value of 5.24 μg/mL, which was lower than indomethacin (24.6 μg/mL). Molecular docking of dihydromorin and crystal structure of MPO showed that dihydromorin had close interaction with key amino acid residues such as Arg239 and Gln91. Antibacterial activity assay showed that only dihydromorin had a strong effect against Streptococcus pyogenes with MIC and MBC values of 15.62 and 31.25 μg/mL, respectively. Conclusions: The results suggest that dihydromorin could be developed as an anti-inflammatory and antibacterial agent. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • BSSCE and Cy3G significantly augmented the glucose uptake in L6 myotubes. • BSSCE and Cy3G modulated glucose uptake via Akt/GLUT4 signal pathway in L6 myotubes. • BSSCE displays potential as a diet approach for diabetes therapy. Abstract In order to illustrate the hypoglycemic mechanism of the dietary anthocyanins from black soybean, the effects of black soybean seed coat extract (BSSCE) and cyanidin-3-O-glucoside (Cy3G), the major anthocyanins of BSSCE on regulation of Akt and GLUT4 in L6 rat skeletal muscle cells were studied. BSSCE and Cy3G significantly augmented the glucose uptake in L6 myotubes in comparison to the normal control (p < 0.05). Especially, at 150 μg/mL of BSSCE and 40 μM of Cy3G treatment, the 2-NBDG uptake level were increased by 1.81-fold and 1.90-fold with that of normal control, respectively. Furthermore, the expressions of p-Akt and GLUT4 were also increased and the GLUT4 translocation was promoted by BSSCE and Cy3G, which indicated the involvement of the Akt/GLUT4 signal pathway in the hypoglycemic mechanism of BSSCE. Overall findings revealed that Cy3G-enriched BSSCE might be a promising functional food or medicine for the treatment of T2DM and its associated metabolic disorder. [ABSTRACT FROM AUTHOR]

Objective: To investigate the in vitro effects of ellagic acid on HIV‐1 replication. Methods: Anti‐HIV‐1 activity of ellagic acid was determined in vitro using X4‐tropic HIV‐1NPO3 and R5‐tropic pBaL Env‐recombinant virus. Anti‐HIV‐1NPO3 activity of ellagic acid was investigated at a multiplicity of infection (MOI) of 0.01. Anti‐HIV‐1 integrase and protease activities of ellagic acid were tested using in vitro integration and proteolytic cleavage assays. Results: Ellagic acid, added either before or after HIV‐1NPO3 exposure, suppressed replication of the virus in C8166 cells up to 34%. Ellagic acid showed an anti‐integrase IC50 of 8.7 μM. No cytotoxicity of ellagic acid at concentrations ranging from 12.5 to 100 μM was observed. Conclusion: We conclude that ellagic acid can inhibit HIV‐1 infection without cytotoxicity. Thus, it may be a new effective agent that has potential to be developed as a novel microbicide against HIV‐1. [ABSTRACT FROM AUTHOR]

Diabetes is a kind of metabolic syndrome (MetS) that seriously threatens human health globally. The leaf of star apple (Chrysophyllum cainito L.) is an incompletely explored folk medicine on diabetes. And, the effects and mechanisms on diabetes complicated glycolipid metabolism disorders are unknown till now. This study aimed to investigate the constituents of star apple leaf polyphenol enriched-fraction (SAP), and elucidate their treatment effects and mechanism on diabetes and accompanied other MetS. The components of SAP were tentatively identified by HPLC-Q-TOF-MS/MS. The antioxidant activity was determined by the scavenging of free radicals and hypoglycemic activities by inhibition of α-glucosidase in vitro. HepG2 cells were used for evaluating the alleviation effects of SAP on lipid accumulation. Streptozotocin and high-fat diet induced diabetic mice were grouped to evaluate the effects of different dosages of SAP. 16S rRNA was conducted to analysis gut microbiome-mediated glucose and lipid metabolism mechanism. It showed that myricitrin was one of the main active constituents of SAP. SAP not only showed low IC50 on -glucosidase (24.427± 0.626 μg/mL), OH·(3.680± 0.054 μg/mL) and ABTS· (9.155±0.234 μg/mL), but significantly induced the lipid accumulation in HepG2 cells (p < 0.05). SAP at 200 mg/kg·day significantly decreased the blood glucose, insulin and oral glucose tolerance test value (p < 0.05). The insulin resistance indexes and oxidative stress were alleviated after administration. SAP not only attenuated hepatic lipid deposition, but also reversed the hepatic glycogen storage. 16S rRNA sequencing results revealed that the interaction between SAP and gut microbiota led to the positive regulation of beneficial bacteria including Akkermansia, Unspecified S24_7, Alistipes and Unspecified_Ruminococcaceae , which might be one of the mechanisms of SAP on MetS. For the first time, this study explored the regulation effect of star apple leaf polyphenols on the hepatic glycolipid metabolism and studied the underlying mechanism from the view of gut microbiota. These findings indicated that SAP possesses great potential to serve as a complementary medicine for diabetes and associated MetS. It provided scientific evidence for folk complementary medicine on the treatment of diabetes-complicated multiple metabolic disorders. [Display omitted] [ABSTRACT FROM AUTHOR]

Rhinacanthins-rich extract (RRE) from Rhinacanthus nasutus leaf and its marker compounds namely rhinacanthin-C, rhinacanthin-D and rhinacanthin-N were evaluated for α-glucosidase inhibitory activity. RRE (IC 50 value of 25.0 µg/mL) exhibited α-glucosidase inhibitory activity almost equivalent to that of rhinacanthin-C (IC 50 value of 22.6 µg/mL) but stronger than that of rhinacanthin-D (IC 50 value of 71.5 µg/mL) and the standard drug, acarbose (IC 50 value of 395.4 µg/mL), while rhinacanthin-N was inactive. Kinetic studies revealed that both RRE and rhinacanthin-C exhibited noncompetitive α-glucosidase inhibitory activity, while combinations of either RRE or rhinacanthin-C with acarbose at low concentrations (¼IC 50 , ½IC 50 and IC 50 ) showed a synergistic inhibitory effect. In silico studies identified the binding mode of rhinacanthin-C highlighting the formation of both polar and apolar contacts of ligand with α-glucosidase. The present study provides the first evidence that RRE containing rhinacanthin-C as the major compound, could find application as an α-glucosidase inhibitor. [ABSTRACT FROM AUTHOR]