Five compounds including a new bisbibenzyl named dendropachol (1) and four known compounds (2–5) comprising 4,5-dihydroxy-2,3-dimethoxy-9,10-dihydrophenanthrene (2), gigantol (3), moscatilin (4) and 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (5) were isolated from a methanolic extract of Dendrobium pachyglossum (Orchidaceae). The chemical structures of the isolated compounds were characterized by spectroscopic methods. Dendropachol (1) was investigated for its protective effects on hydrogen peroxide (H₂O₂)-induced oxidative stress in HaCaT keratinocytes. Compound 1 showed strong free radical scavenging compared to the positive control. For the cytoprotective effect, compound 1 increased the activities of GPx and CAT and the level of GSH but reduced intracellular reactive oxygen species (ROS) generation and accumulation. In addition, compound 1 significantly diminished the expression of p53, Bax, and cytochrome C proteins, decreased the activities of caspase-3 and caspase-9, and increased Bcl-2 protein. The results suggested that compound 1 exhibited antioxidant activities and protective effects in keratinocytes against oxidative stress induced by H₂O₂.

Kratom (Mitragyna speciosa (Korth.) Havil.) has been used to reduce blood sugar and lipid profiles in traditional medicine, and mitragynine is a major constituent in kratom leaves. Previous data on the blood sugar and lipid-altering effects of kratom are limited. In this study, phytochemical analyses of mitragynine, 7-hydroxymitragynine, quercetin, and rutin were performed in kratom extracts. The effects on α-glucosidase and pancreatic lipase activities were investigated in kratom extracts and mitragynine. The LC-MS/MS analysis showed that the mitragynine, quercetin, and rutin contents from kratom extracts were different. The ethanol extract exhibited the highest total phenolic content (TPC), total flavonoid content (TFC), and total alkaloid content (TAC). Additionally, compared to methanol and aqueous extracts, the ethanol extract showed the strongest inhibition activity against α-glucosidase and pancreatic lipase. Compared with the anti-diabetic agent acarbose, mitragynine showed the most potent α-glucosidase inhibition, with less potent activity of pancreatic lipase inhibition. Analysis of α-glucosidase and pancreatic lipase kinetics revealed that mitragynine inhibited noncompetitive and competitive effects, respectively. Combining mitragynine with acarbose resulted in a synergistic interaction with α-glucosidase inhibition. These results have established the potential of mitragynine from kratom as a herbal supplement for the treatment and prevention of diabetes mellitus.

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.

Mitragynine (MG) is an indole alkaloid found in the extract of Mitragyna speciosa Korth native to Southeast Asia. Although MG is known for its pain-relieving and psychoactive effects, reports have suggested that it has therapeutic potential against neoplasms and psychiatric disorders. However, no evidence currently exists to support the effect of MG on brain tumors. This study aimed to investigate the antitumor effects of MG in C6 rat glioma and SH-SY5Y human neuroblastoma tumor cell lines compared with those in the non-tumor HT22 mouse hippocampal neuronal cell line. MTT assay for cell viability, clonogenic and wound healing assays for cell migration, Hoechst 33342/propidium iodide staining for nuclear morphology, and cell cycle distribution using flow cytometry were performed. MG at 125.47 μM (50 μg/ml) significantly reduced the viability of all cell lines, and the clonogenicity of C6 glioma cells began decreasing at 75.28 μM (30 μg/ml) of MG. Cell migration was inhibited in C6 and HT22 cells treated with 75.28 μM (30 μg/ml) of MG. Apoptotic nuclear condensation and fragmentation were observed in all cell lines treated with 125.47 μM (50 μg/ml) MG, whereas late-phase apoptotic cells were predominant in the group treated with 250.94 μM (100 μg/ml) of MG. The cell cycle assay results suggest that MG arrested the S phase in the C6 cell line and the G2/M phase in the HT22 cell lines. This study showed that MG induces cell death and cell cycle arrest, disrupting cell migration and reducing the clonogenicity of brain tumor cells.

Although many natural products have proven their potential to regulate obesity through the modulation of adipocyte biology, none of them has yet been approved for clinical use in obesity therapy. This work aims to isolate valuable secondary metabolites from an orchid species (Dendrobium heterocarpum) and evaluate their possible roles in the growth and differentiation of 3T3-L1 pre-adipocytes. Six compounds were isolated from the orchid’s methanolic extracts and identified as amoenylin (1), methyl 3-(4-hydroxyphenyl) propionate (2), 3,4-dihydroxy-5,4’-dimethoxybibenzyl (3), dendrocandin B (4), dendrofalconerol A (5), and syringaresinol (6). Among these phytochemicals, compounds 2, 3, and 6 exhibited lower effects on the viability of 3T3-L1 cells, offering non-cytotoxic concentrations of ≲10 µM. Compared to others tested, compound 3 was responsible for the maximum reduction of lipid storage in 3T3-L1 adipocytes (IC₅₀ = 6.30 ± 0.10 µM). A set of protein expression studies unveiled that compound 3 at non-cytotoxic doses could suppress the expression of some key transcription factors in adipocyte differentiation (i.e., PPARγ and C/EBPα). Furthermore, this compound could deactivate some proteins involved in the MAPK pathways (i.e., JNK, ERK, and p38). Our findings prove that D. heterocarpum is a promising source to explore bioactive molecules capable of modulating adipocytic growth and development, which can potentially be assessed and innovated further as pharmaceutical products to defeat obesity.