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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.

Background: Since cannabis has been legally allowed for medicinal purposes in many countries, it has become the most interesting issue, particularly in neurologic disorders, such as Alzheimer’s disease (AD). Inhibition of acetylcholinesterase (AChE) is one of the mechanisms for the treatment of AD. Objectives: The present study aimed to establish a method for the preparation of cannabinoid-rich extracts and determine their AChE inhibitory activity. Methods: The cannabinoid-rich extracts were prepared through a green extraction process using microwave-assisted extraction (MAE) followed by hydrophobic column separation. The contents of cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC) were determined using high-performance liquid chromatography (HPLC). In vitro AChE inhibitory activity was determined via the photometric method using AChE from Electrophorus electricus. Results: Three cannabinoids-rich fractions were obtained with different concentrations of CBD and THC, namely Fractions I (CBD of 8.1% w/w; THC of 52.2% w/w), II (CBD of 9.2% w/w; THC of 8.0% w/w), and III (CBD 1.3% w/w, THC 33.5% w/w). These cannabinoid-rich extracts exhibited AChE inhibitory activity, with IC50 values of 52.3, 59.8, and 71.2 µg/mL, respectively. Conclusion: This finding suggests that CBD, but not THC, might be an active compound contributing to AChE inhibitory effect.

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.

Objective: The purpose of this study was to (i) synthesize and develop an alkynyloxy derivative of lawsone as an antifungal spray and (ii) assess the antifungal spray’s effectiveness in reducing the viability of Candida albicans (C. albicans) on polymethylmethacrylate (PMMA) specimens. Methods: Lawsone methyl ether (LME) and its derivative, 2-(prop-2-ynyloxy)naphthalene-1,4-dione (compound 1) were synthesized and characterized. The synthetic compounds were screened for antimicrobial activities against C. albicans using the microtiter broth dilution method to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Compound 1 was further formulated as an antifungal spray in three concentrations (100, 200, and 400 μg/mL). C. albicans biofilms were developed for 48 h on PMMA specimens. The efficacy of using an antifungal spray for 1 and 3 min to remove biofilm was assessed using colony counting and scanning electron microscopy (SEM). Chlorhexidine gluconate (CHX), polident®, and distilled water were used as positive and negative control cleansing solutions, respectively. Results: LME and compound 1 showed comparable inhibition against C. albicans with a MIC of 25 μg/mL and MFC of 50 μg/mL. For immediate treatment, C. albicans was not detected on PMMA specimens when expose to 2% CHX and compound 1 (100, 200, and 400 μg/mL) antifungal spray for 3 min. However, after recolonization, a small number of viable cells were observed in denture soaked in compound 1 antifungal spray for 3 min group. Following recolonization, polident® and distilled water had comparable viable cell counts of C. albicans to the no treatment group. Scanning electron microscope (SEM) images revealed that CHX, polident®, and compound 1 caused cell damage in various forms. Conclusion: Denture spray containing synthetic alkynyloxy derivative of lawsone is a promising antifungal agent for C. albicans biofilm removal from the PMMA surface.

Curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are the major active compounds found in Curcuma longa L. (turmeric). Although their suppressive effects on bone resorption have been demonstrated, their pharmacokinetic disadvantages remain a concern. Herein, we utilized solid dispersion of a curcuminoid-rich extract (CRE), comprising such curcuminoids, to prepare CRE-SD; subsequently, we performed liposome encapsulation of the CRE-SD to yield liposomal CRE-SD. In vitro release assessment revealed that a lower cumulative mass percentage of CRE-SD was released from liposomal CRE-SD than from CRE-SD samples. After culture of murine RANKL-stimulated RAW 264.7 macrophages, our in vitro examinations confirmed that liposomal CRE-SD may impede osteoclastogenesis by suppressing p65 and IκBα phosphorylation, together with nuclear translocation and transcriptional activity of phosphorylated p65. Blind docking simulations showed the high binding affinity between curcuminoids and the IκBα/p50/p65 protein complex, along with many intermolecular interactions, which corroborated our in vitro findings. Therefore, liposomal CRE-SD can inhibit osteoclastogenesis via the canonical NF-κB signaling pathway, suggesting its pharmacological potential for treating bone diseases with excessive osteoclastogenesis.

Our previous study uncovered potent inhibitory effects of two naphthoquinones from Impatiens balsamina, namely lawsone methyl ether (2-methoxy-1,4-naphthoquinone, LME) and lawsone (2-hydroxy-1,4-naphthoquinone), against α-glucosidase. This gave us the insight to compare the hypoglycemic and hypolipidemic effects of LME and lawsone in high-fat/high-fructose-diet- and nicotinamide-streptozotocin-induced diabetic rats for 28 days. LME and lawsone at the doses of 15, 30, and 45 mg/kg, respectively, produced a substantial and dose-dependent reduction in the levels of fasting blood glucose (FBG), HbA1c, and food/water intake while boosting the insulin levels and body weights of diabetic rats. Additionally, the levels of total cholesterol (TC), triglycerides (TGs), high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), aspartate transaminase (AST), alanine transaminase (ALT), creatinine, and blood urea nitrogen (BUN) in diabetic rats were significantly normalized by LME and lawsone, without affecting the normal rats. LME at a dose of 45 mg/kg exhibited the most potent antihyperglycemic and antihyperlipidemic effects, which were significantly comparable to glibenclamide but higher than those of lawsone. Furthermore, the toxicity evaluation indicated that both naphthoquinones were entirely safe for use in rodent models at doses ≤ 50 mg/kg. Therefore, the remarkable antihyperglycemic and antihyperlipidemic potentials of LME make it a promising option for future drug development.

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.

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.

Ginger rhizome, a common spice that has been traditionally used in various health aspects. The rhizome contains volatile oil and nonvolatile oil compounds, including oleoresin. Chemical constituents of ginger are numerous and vary depending on the geographic origin, harvest process, and storage conditions. [6]-Gingerol, a major bioactive constituent of ginger, has been reported to possess anti-inflammatory, antiviral, antitumor, antioxidant, and antiemetic effects. Therefore, it is a valuable food molecule with benefits for human health. This review summarized current findings on [6]-gingerol with regards to its beneficial effects on human health, encompassing the biological activities, mechanisms of action and toxicity assessment. In addition, relevant evidence in support of the application of [6]-gingerol towards the promotion health and vitality, as well as methods for extraction, identification and quantitative determination of [6]-gingerol are also provided.

Aims: Curcuminoid (CRE-Ter) is the active component of turmeric, and is widely understood to offer anticancer, antioxidant, and anti-inflammatory properties. The drawbacks, however, include rapid metabolism and systemic elimination as well as minimal bioavailability. In an attempt to address the issue of bioavailability, this study seeks to encapsulate CRE-Ter in a liposome before its incorporation on PLA foams in order to inhibit the process of osteoclastogenesis which takes place in RANKL-induced RAW 264.7 cells. Main methods: Having encapsulated the CRE-Ter into the liposomes, the influence of the release of liposomal CRE-Ter from PLA foams in order to inhibit the process of osteoclastogenesis in the case of RANKL-induced RAW 264.7 cells was investigated. By measuring the decline in tartrate-resistant acid phosphatase (TRAP) content it was possible to evaluate the influence of CRE-Ter/Liposome upon osteoclastogenesis in vitro. Immunocytochemistry was employed to assess the marker for the monocyte/macrophage cells F4/80 content, while Western blots were used to evaluate the underlying mechanisms involved. Key findings: The findings demonstrate a novel method which employs tissue engineering scaffolds, which are produced to work alongside advanced additive manufacturing techniques with their basis in concepts from the field of alternative medicine. Initially, it was confirmed that CRE-Ter/Liposome at 20 μg/ml is able to inhibit the creation of multinucleated osteoclasts which are induced by the receptor activator of the nuclear factor-κB ligand (RANKL) in RAW 264.7 cells. It was shown that the CRE-Ter/liposome was able to increase the F4/80 content (F4/80 immunohistochemistry) in the RANKL treated RAW 264.7 cells. The TRAP content was lowered by the CRE-Ter/liposome along with the osteoclast-specific gene content such as cathepsin K, via the use of liposome-encapsulated PLA foams. When treated with CRE-Ter/liposome, RANKL-induced NF-κB and ERK components such as NF-κB-p65, ERK, phospho-NF-κB-p65, and phospho-ERK pathways were all suppressed. Significance: The successful encapsulation of CRE-Ter into the liposomes offered a new opportunity to provide a new inhibitor of osteoclastogenesis and offers the possibility of developing treatments capable of addressing diseases which concern abnormal bone lysis.

The number of patients with type 2 diabetes mellitus (T2DM) has increased worldwide. Although an instant cure was achieved with the standard treatment acabose, unsatisfactory symptoms associated with cardiovascular disease after acabose administration have been reported. Therefore, it is important to explore new treatments. A Thai folk recipe has long been used for T2DM treatment, and it effectively decreases blood glucose. However, the mechanism of this recipe has never been proven. Therefore, the potential anti-T2DM effect of this recipe, which is used in Thai hospitals, was determined to involve alpha-glucosidase (AG) inhibition with a half maximal inhibitory concentration (IC50). In vitro experiments showed that crude Cinnamomum verum extract (IC50 = 0.35 ± 0.12 mg/mL) offered excellent inhibitory activity, followed by extracts from Tinospora crispa (IC50 = 0.69 ± 0.39 mg/mL), Stephania suberosa (IC50 = 1.50 ± 0.17 mg/mL), Andrographis paniculate (IC50 = 1.78 ± 0.35 mg/mL), and Thunbergia laurifolia (IC50 = 4.66 ± 0.27 mg/mL). However, the potencies of these extracts were lower than that of acabose (IC50 = 0.55 ± 0.11 mg/mL). Therefore, this study investigated and developed a formulation of this recipe using computational docking. Among 61 compounds, 7 effectively inhibited AG, including chlorogenic acid (IC50 = 819.07 pM) through 5 hydrogen bonds (HBs) and 2 hydrophobic interactions (HIs); β-sitosterol (IC50 = 4.46 nM, 6 HIs); ergosterol peroxide (IC50 = 4.18 nM, 6 HIs); borapetoside D (IC50 = 508.63 pM, 7 HBs and 2 HIs); borapetoside A (IC50 = 1.09 nM, 2 HBs and 2 His), stephasubimine (IC50 = 285.37 pM, 6 HIs); and stephasubine (IC50 = 1.09 nM, 3 HBs and 4 HIs). These compounds bind with high affinity to different binding pockets, leading to additive effects. Moreover, the pharmacokinetics of six of these seven compounds (except ergosterol peroxide) showed poor absorption in the gastrointestinal tract, which would allow for competitive binding to AG in the small intestine. These results indicate that the development of these 6 compounds into oral antidiabetic agents is promising.

Abstract The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure–activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α‐mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram‐positive bacteria, but also restore the susceptibility of colistin against Gram‐negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance.

miR-21 expression stimulates osteoclast cells in the context of osteoclastogenesis. A previous report showed that NFκB-miR-21 pathway could serve as an innovative alternative to devise therapeutics for healing diabetic ulcers. Furthermore, our study demonstrated that a highly water-soluble curcuminoids-rich extract (CRE-Ter) inhibits osteoclastogenesis through NFκB pathway. The interplay between miR-21 and CRE-Ter in osteoclastogenesis has not yet been investigated. In this study, we examined the relation of CRE-Ter and miR-21 gene expression in receptor of the nuclear factor κB (NFκB) ligand (RANKL) - induced murine monocyte/macrophage RAW 264.7 cells, osteoclast cells, in osteoclastogenesis. Effect of CRE-Ter on generation of intracellular reactive oxygen species (ROS) was estimated by dichlorofluorescein diacetate (DCFH-DA). The results reveal that CRE-Ter reduced expression levels of miR-21 gene in osteoclasts. The inhibitory effects of CRE-Ter on in vitro osteoclastogenesis were evaluated by reduction in tartrate-resistant acid phosphatase (TRAP) content, and by reduction in expression levels of an osteoclast-specific gene, cathepsin K. Treatment of the osteoclast cells with CRE-Ter suppressed RANKL-induced NFκB activation including phospho-NFκB-p65, and phospho IκBα proteins. Western blot analysis revealed that NFκB inhibitor up-regulated CRE-Ter-promoted expression of phospho-NFκB-p65. In addition, CRE-Ter dose-dependently inhibited phospho-Akt expression. CRE-Ter also dose-dependently reduced DNA binding activity of NFκB and Akt as revealed by EMSA. ChIP assay revealed binding of NFκB-p65 to miR-21 promoters. In conclusion, our results demonstrate that CRE-Ter downregulates miR-21 gene expression in osteoclasts via a de novo mechanism, NFκB- Akt-miR-21 pathway.

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

Background: Sarcopenia is a disease of progressive loss of muscle mass due to the imbalance of protein synthesis and proteolysis, and tends to emerge with ageing. Currently its treatment consists of non-drug therapies and drug therapies, but some medications can have various side effects. Therefore, it is important to search for effective herbal medicines that can modulate muscle mass. Purpose: In this study, we investigated the inhibition effects of Cu, De, Bis, CRE, CRE-SD, CRE-Bin, and CRE-Ter on dexamethasone-induced muscle atrophy in differentiation of C2C12 cells. Methods: C2C12 cells were cultured and treated with various concentrations of curcuminoids including, Cu, De, Bis, CRE, CRE-SD, CRE-Bin, and CRE-Ter. The inhibitory effects were studied using various methods, including MTT and LDH assays for cell viability and cell cytotoxicity, RT-qPCR for gene expression analysis, and Western blots for protein analysis. In this study, dexamethasone-treated C2C12 myotubes (Dex) are the positive drug control and used as in vitro models of muscle atrophy. Results: The results revealed that treating differentiated C2C12 cells with Cu, CRE, CRE-Bin, and CRE-Ter reduced Atrogin-1 and MuRF-1 expression, whereas CRE-SD reduced only MuRF-1 expression. The Western blot analysis results show that Cu, CRE, CRE-Bin, CRE-Ter, and CRE-SD upregulated the phosphorylation level of Akt, which is an important protein in the mTOR signaling pathway. Conclusion: Our results show that Cu, CRE, CRE-Bin, CRE-SD, and CRE-Ter tend to inhibit muscle atrophy by decreasing expression of Atrogin-1 and MuRF-1 inhibiting protein degradation, and to upregulate Phospho-Akt to stimulate protein synthesis. These results provide corroborating evidence of therapeutic potential to treat sarcopenia patients.

Neurodegenerative diseases present an increasing problem as the world’s population ages; thus, the discovery of new drugs that prevent diseases such as Alzheimer’s, and Parkinson’s diseases are vital. In this study, Rhinacanthin-C and -D were isolated from Rhinacanthus nasustus, using ethyl acetate, followed by chromatography to isolate Rhinacanthin-C and -D. Both compounds were confirmed using NMR and ultra-performance-LCMS. Using glutamate toxicity in HT-22 cells, we measured cell viability and apoptosis, ROS build-up, and investigated signaling pathways. We show that Rhinacanthin-C and 2-hydroxy-1,4-naphthoquinone have neuroprotective effects against glutamate-induced apoptosis in HT-22 cells. Furthermore, we see that Rhinacanthin-C resulted in autophagy inhibition and increased ER stress. In contrast, low concentrations of Rhinacanthin-C and 2-hydroxy-1,4-naphthoquinone prevented ER stress and CHOP expression. All concentrations of Rhinacanthin-C prevented ROS production and ERK1/2 phosphorylation. We conclude that, while autophagy is present in HT-22 cells subjected to glutamate toxicity, its inhibition is not necessary for cryoprotection.

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 (IC50 value of 25.0 µg/mL) exhibited α-glucosidase inhibitory activity almost equivalent to that of rhinacanthin-C (IC50 value of 22.6 µg/mL) but stronger than that of rhinacanthin-D (IC50 value of 71.5 µg/mL) and the standard drug, acarbose (IC50 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 (¼IC50, ½IC50 and IC50) 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.

A methanolic extract from Solanum torvum fruits exhibited inhibitory activity against the angiotensin-converting enzyme (ACE) with an IC50 value of 1.2 mg/mL. On the basis of a bioassay-guided isolation, an ACE inhibitory active compound, namely (E)-2,3-dihydroxycyclopentyl-3-(3′,4′-dihydroxyphenyl)acrylate (1) (IC50 of 778 µg/mL), was obtained, together with a novel methyl salicylate glycoside – torvumoside [methyl salicylate 2-O-(2′-O-β-apiofuranosyl, 6′-O-β-xylopyranosyl)-β-glucopyranoside] (3) and a known compound, lariciresinol-4,4′-O-β-D-diglucoside (2). This is the first report of these compounds in this plant.