ABSTRACT
Eight compounds, including one anthraquinone, two bibenzyls, one phenanthrene, three dihydrophenanthrenes, and one flavonoid, were isolated from the roots of Dendrobium polyanthum Wall. ex Lindl. Among these, six compounds were investigated for inhibitory activities against alpha-glucosidase, alpha-amylase, and advanced glycation end products (AGEs) production. Additionally, molecular docking was conducted to analyze the interactions of the test compounds with alpha-glucosidase. Moscatin, the only isolated phenanthrene, displayed the strongest anti-alpha-glucosidase activity with an IC50 of 32.45 ± 1.04 µM, approximately 10-fold smaller than that of acarbose. Furthermore, moscatilin most strongly inhibited alpha-amylase and AGEs production with IC50 values of 256.94 ± 9.87 and 67.89 ± 9.42 µM, respectively. Molecular docking analysis revealed the effective binding of all substances to alpha-glucosidase with smaller lowest binding energy values than acarbose. Moscatin was selected for kinetics studies, and it was identified as a non-competitive inhibitor with approximately 9-fold greater inhibitory capability than acarbose. This study represents the first report on the phytochemical constituents and antidiabetic potential of compounds derived from the roots of D. polyanthum Wall. ex Lindl.
ABSTRACT
Astaxanthin is a powerful antioxidant known to enhance skin, cardiovascular, eye, and brain health. In this study, the genome insights and astaxanthin production of two newly isolated astaxanthin-producing yeasts (TL35-5 and PL61-2) were evaluated and compared. Based on their phenotypic and genotypic characteristics, TL35-5 and PL61-2 were identified as basidiomycetous yeasts belonging to Rhodotorula paludigena and Rhodotorula sampaioana, respectively. To optimize astaxanthin production, the effects of cultural medium composition and cultivation conditions were examined. The optimal conditions for astaxanthin production in R. paludigena TL35-5 involved cultivation in AP medium containing 10 g/L glucose as the sole carbon source, supplemented with 1.92 g/L potassium nitrate, pH 6.5, and incubation at 20°C for 3 days with shaking at 200 rpm. For R. sampaioana PL61-2, the optimal medium composition for astaxanthin production consisted of AP medium with 40 g/L glucose, supplemented with 0.67 g/L urea, pH 7.5, and the fermentation was carried out at 20°C for 3 days with agitating at 200 rpm. Under their optimal conditions, R. paludigena TL35-5 and R. sampaioana PL61-2 gave the highest astaxanthin yields of 3.689 ± 0.031 and 4.680 ± 0.019 mg/L, respectively. The genome of TL35-5 was 20,982,417 bp in length, with a GC content of 64.20%. A total of 6,789 protein-encoding genes were predicted. Similarly, the genome of PL61-2 was 21,374,169 bp long, with a GC content of 64.88%. It contained 6,802 predicted protein-encoding genes. Furthermore, all essential genes involved in astaxanthin biosynthesis, including CrtE, CrtYB, CrtI, CrtS, and CrtR, were identified in both R. paludigena TL35-5 and R. sampaioana PL61-2, providing evidence for their ability to produce astaxanthin.
Subject(s)
Rhodotorula , Xanthophylls , Xanthophylls/metabolism , Rhodotorula/genetics , Rhodotorula/metabolism , Fermentation , Genomics/methods , Culture Media/chemistry , Genome, Fungal , PhylogenyABSTRACT
Dendroochreatene (1), a new phenanthrene derivative with a spirolactone ring, was isolated from the whole Dendrobium ochreatum plant together with 11 known compounds (2-12). The structure of the new compound was elucidated spectroscopically and phenolic compounds were firstly reported from D. ochreatum. Moscatilin (4), major compound isolated from D. ochreatum, was found to be cytotoxic toward H460 lung-cancer cells, with an IC50 value of 147.3 ± 0.9 µM, while loddigesiinol C (7), C-α-methoxy derivative was inactive.
ABSTRACT
Background: The upgrade of natural products for cancer treatment is essential since current anticancer drugs still pose severe side effects. Cymensifin A (Cym A) isolated from an orchid Cymbidium ensifolium has shown its potential to induce the death of several cancer cells; however, its underlying molecular mechanisms are hitherto unknown. Methods: Here, we conducted a set of in vitro preliminary tests to assess the cytotoxic effects of Cym A on non-small-cell lung cancer (NSCLC) cells (A549, H23, H292, and H460). A flow cytometry system and Western blot analyses were employed to unveil molecular mechanisms underlying cancer cell apoptosis caused by Cym A. Results: Cym A at 25-50 µM caused the death of all NSCLC cells tested, and its cytotoxicity was comparable to cisplatin, a currently used anticancer drug. The compound induced apoptosis of all NSCLC cells in a dose-dependent manner (5-50 µM), proven by flow cytometry, but H460 cells showed more resistance compared to other cells tested. Cym A-treated H460 cells demonstrated increased reactive oxygen species (ROS) and downregulated antioxidants (catalase, superoxide dismutase, and thioredoxin). The compound also upregulated the tumor suppressor P53 and the pro-apoptotic protein BAX but downregulated pro-survival proteins (BCL-2 and MCL-1) and deactivated survival signals (AKT and ERK) in H460 cells. Cym A was proven to trigger cellular ROS formation, but P53 and BAX were 2-fold more activated by Cym A compared to those treated with hydrogen peroxide. Our findings also supported that Cym A exerted its roles in the downregulation of nuclear factor erythroid 2-related factor 2 (a regulator of cellular antioxidant activity) and the increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase 3/7 during apoptosis. Conclusion: We propose that Cym A induces lung cancer cell death via ROS-mediated apoptosis, while the modulation of cellular ROS/antioxidant activity, the upregulation of P53 and BAX, the downregulation or deactivation of BCL-2, MCL-1, AKT, and ERK, and the increased cleavage of PARP and caspase 3/7, were the elucidated underlying molecular mechanisms of this phytochemical. The compound can be a promising candidate for future anticancer drug development.
ABSTRACT
The phytochemical investigation of the whole plants of Coelogyne fuscescens Lindl. var. brunnea led to the discovery of three new phenolic glycosides, i.e., coelofusides A-C (1-3) and 12 known compounds (4-15). For the first time, we reported the nuclear magnetic resonance (NMR) data of 4-O-(6'-O-glucosyl-4â³-hydroxybenzoyl)-4-hydroxybenzyl alcohol (4) in this study. The identification of the structures of newly discovered compounds was done through the analysis of their spectroscopic data [NMR, mass spectrometry, ultraviolet, Fourier transform infrared, optical rotation, and circular dichroism (CD)]. In comparison to anticancer drugs (i.e., etoposide and carboplatin), we evaluated anticancer potential of the isolated compounds on two different breast cancer cell lines, namely, T47D and MDA-MB-231. Human fibroblast HaCaT cells were used as the control cells. After a 48 h incubation, flavidin (8), coelonin (10), 3,4-dihydroxybenzaldehyde (11), and oxoflavidin (12) showed significant cytotoxic effects against breast cancer cells. Among them, oxoflavidin (12) exhibited the most potent cytotoxicity on MDA-MB-231 with an IC50 value of 26.26 ± 4.33 µM. In the nuclear staining assay, oxoflavidin induced apoptosis after 48 h in both T47D and MDA-MB-231 cells in a dose-dependent manner. Furthermore, oxoflavidin upregulated the expression of apoptotic genes, such as p53, Bax, poly(ADP-ribose) polymerase, caspase-3, and caspase-9 genes while significantly decreasing antiapoptotic protein (Bcl-2) expression levels.
ABSTRACT
Dendrobium plants are widely used in traditional Chinese medicine. Their secondary metabolites such as bibenzyls and phenanthrenes show various pharmacological benefits such as immunomodulation and inhibitory effects on cancer cell growth. However, our previous study also showed that some of these promising compounds (i.e., gigantol and cypripedin) also induced the expression of inflammatory cytokines including TNF in human monocytes, and thus raising concerns about the use of these compounds in clinical application. Furthermore, the effects of these compounds on other immune cell populations, apart from monocytes, remain to be investigated. In this study, we evaluated immunomodulatory effects of seven known bibenzyl compounds purified from Dendrobium species in human peripheral blood mononuclear cells (PBMCs) that were stimulated with lipopolysaccharide (LPS). Firstly, using flow cytometry, moscatilin (3) and crepidatin (4) showed the most promising dose-dependent immunomodulatory effects among all seven bibenzyls, determined by significant reduction of TNF expression in LPS-stimulated CD14+ monocytes. Only crepidatin at the concentration of 20 µM showed a significant cytotoxicity, i.e., an increased cell death in late apoptotic state. In addition, deep immune profiling using high-dimensional single-cell mass cytometry (CyTOF) revealed broad effects of Dendrobium compounds on diverse immune cell types. Our findings suggest that to precisely evaluate therapeutic as well as adverse effects of active natural compounds, a multi-parameter immune profiling targeting diverse immune cell population is required.
Subject(s)
Bibenzyls , Dendrobium , Humans , Leukocytes, Mononuclear , Lipopolysaccharides/pharmacology , Bibenzyls/pharmacology , Cell Line, TumorABSTRACT
BACKGROUND: Curcuminoids, including curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin, are natural polyphenolic compounds that exhibit various biological properties, such as antioxidant, anti-inflammatory, and anticancer activities. Dysregulation of the interleukin (IL)-6-mediated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway is closely associated with the development of colorectal cancer (CRC). METHODS: Here, we have evaluated the modulation of the IL-6/JAK/STAT3 pathway of curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin in LoVo and HT-29 colorectal cancer cells with a single molecular array (Simoa), western blot analysis, real-time polymerase chain reaction (PCR), and pathway analysis system. RESULTS: The study showed that curcuminoids suppressed the amount of IL-6 in LoVo and HT-29 colorectal cancer cells. Meanwhile, curcuminoids inhibited the expression of inflammation regulator-related microRNA (miRNA). We also found that the expression of total STAT3 was downregulated by curcuminoids. Moreover, the pathway analysis system showed that curcuminoids inactivated the JAK/STAT3 signaling pathway. Taken together, we demonstrated that the anti-cancer activities of curcuminoids against colorectal cancer are due to the modulation of the IL-6/JAK/STAT3 cascade. CONCLUSION: Curcuminoids could be a promising anti-cancer agent for the treatment of human colorectal cancer.
Subject(s)
Colorectal Neoplasms , Curcumin , Humans , Janus Kinases , Curcumin/pharmacology , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Interleukin-6/metabolism , Diarylheptanoids , Signal Transduction , Colorectal Neoplasms/metabolismABSTRACT
Astaxanthin is a carotenoid known for its powerful antioxidant properties. This study focused on isolating yeast strains capable of producing astaxanthin from flower and fruit samples collected in Thailand. Out of 115 isolates, 11 strains were identified that produced astaxanthin. Molecular identification techniques revealed that these isolates belonged to two species: Rhodotorula paludigena (5 isolates) and Rhodosporidiobolus ruineniae (6 isolates). Whole-genome analysis of one representative strain, R. paludigena SP9-15, identified putative candidate astaxanthin synthesis-associated genes, such as CrtE, CrtYB, CrtI, CrtS, CrtR, CrtW, CrtO, and CrtZ. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) confirmed astaxanthin production. Further optimization of astaxanthin production was carried out by investigating the effects of various factors on the growth rate and astaxanthin production. The optimal conditions were 40 g/L glucose as a carbon source, pH 7.5, and cultivation at 25 °C with 200 rpm for 3 days. Under these conditions, R. paludigena SP9-15 synthesized biomass of 11.771 ± 0.003 g/L, resulting in astaxanthin with a content of 0.558 ± 0.018 mg/g DCW (dry cell weight), an astaxanthin yield of 6.565 ± 0.238 mg/L, and astaxanthin productivity of 2.188 ± 0.069 g/L/day. These findings provide insights into astaxanthin production using red yeast strains from Thailand and highlight the potential of R. paludigena SP9-15 for further application.
ABSTRACT
Bacterial meningitis remains one of the most prevalent infectious diseases worldwide. Although advances in medical care have improved mortality and morbidity, neurological complications remain high. Therefore, aside from antibiotics, therapeutic adjuvants targeting neuroinflammation are essential to combat the long-term neuronal sequelae of bacterial meningitis. In the present study, we propose (-)-dendroparishiol as a potential add-on therapy to improve neuroinflammation associated with bacterial meningitis. The biological activity of (-)-dendroparishiol was first predicted by computational analysis and further confirmed in vitro using a cell-based assay with LPS-induced BV-2 microglial cells. Biological pathways involved with (-)-dendroparishiol were identified by applying network pharmacology. Computational predictions of biological activity indicated possible attenuation of several inflammatory processes by (-)-dendroparishiol. In LPS-induced BV-2 microglial cells, (-)-dendroparishiol significantly reduced the expression of inflammatory mediators: iNOS, NO, COX-2, IL-6, and TNF-α. Molecular docking results demonstrated the potential iNOS and COX-2 inhibitory activity of (-)-dendroparishiol. Network pharmacological analysis indicated the plausible role of (-)-dendroparishiol in biological processes involved in oxidative stress and neuroinflammation with enrichment in neuroinflammatory pathways. Overall, this study provides scientific evidence for the potential application of (-)-dendroparishiol in the management of bacterial meningitis-associated neuroinflammation.
Subject(s)
Inflammation , Meningitis, Bacterial , Humans , Inflammation/metabolism , Neuroinflammatory Diseases , Lipopolysaccharides/adverse effects , Molecular Docking Simulation , Network Pharmacology , Microglia/metabolism , Meningitis, Bacterial/metabolism , NF-kappa B/metabolismABSTRACT
Three new phenanthrene derivatives (1, 2, 4), one new fluorenone (3), and four known compounds (5-8) were isolated from the ethyl acetate extract of Dendrobium crumenatum Sw. stems using column chromatography. The chemical structures were elucidated by analysis of spectroscopic data. The absolute configuration of 4 was determined by electronic circular dichroism calculation. We also evaluated the immunomodulatory effects of compounds isolated from D. crumenatum in human peripheral blood mononuclear cells from healthy individuals and those from patients with multiple sclerosis in vitro. Dendrocrumenol B (2) and dendrocrumenol D (4) showed strong immunomodulatory effects on both CD3+ T cells and CD14+ monocytes. Compounds 2 and 4 could reduce IL-2 and TNF production in T cells and monocytes that were treated with phorbol-12-myristate-13-acetate and ionomycin (PMA/Iono). Deep immune profiling using high-dimensional single-cell mass cytometry could confirm immunomodulatory effects of 4, quantified by the reduction of activated T cell population under PMA/Iono stimulation, in comparison to the stimulated T cells without treatment.
Subject(s)
Dendrobium , Phenanthrenes , Humans , Dendrobium/chemistry , Leukocytes, Mononuclear , Monocytes , Phenanthrenes/pharmacology , Phenanthrenes/chemistry , T-Lymphocytes , Tetradecanoylphorbol Acetate/pharmacology , Fluorenes/chemistry , Fluorenes/pharmacologyABSTRACT
Central nervous system (CNS) diseases are a significant health burden globally, with the development of novel drugs lagging behind clinical needs. Orchidaceae plants have been traditionally used to treat CNS diseases, leading to the identification of therapeutic leads against CNS diseases from the Aerides falcata orchid plant in the present study. The study isolated and characterized ten compounds, including a previously undescribed biphenanthrene derivative, Aerifalcatin (1), for the first time from the A. falcata extract. The novel compound 1 and known compounds, such as 2,7-dihydroxy-3,4,6-trimethoxyphenanthrene (5), agrostonin (7), and syringaresinol (9), showed potential activity in CNS-associated disease models. Notably, compounds 1, 5, 7, and 9 demonstrated the ability to alleviate LPS-induced NO release in BV-2 microglial cells, with IC50 values of 0.9, 2.5, 2.6, and 1.4 µM, respectively. These compounds also significantly inhibited the release of pro-inflammatory cytokines, IL-6 and TNF-α, reflecting their potential anti-neuroinflammatory effects. Additionally, compounds 1, 7, and 9 were found to reduce cell growth and migration of glioblastoma and neuroblastoma cells, indicating their potential use as anticancer agents in the CNS. In summary, the bioactive agents isolated from the A. falcata extract offer plausible therapeutic options for CNS diseases.
ABSTRACT
The root of Boesenbergia rotunda, a culinary plant commonly known as fingerroot, has previously been reported to possess anti-obesity activity, with four flavonoids identified as active principles, including pinostrobin, panduratin A, cardamonin, and isopanduratin A. However, the molecular mechanisms underlying the antiadipogenic potential of isopanduratin A remain unknown. In this study, isopanduratin A at non-cytotoxic concentrations (1-10 µM) significantly suppressed lipid accumulation in murine (3T3-L1) and human (PCS-210-010) adipocytes in a dose-dependent manner. Downregulation of adipogenic effectors (FAS, PLIN1, LPL, and adiponectin) and adipogenic transcription factors (SREBP-1c, PPARγ, and C/EBPα) occurred in differentiated 3T3-L1 cells treated with varying concentrations of isopanduratin A. The compound deactivated the upstream regulatory signals of AKT/GSK3ß and MAPKs (ERK, JNK, and p38) but stimulated the AMPK-ACC pathway. The inhibitory trend of isopanduratin A was also observed with the proliferation of 3T3-L1 cells. The compound also paused the passage of 3T3-L1 cells by inducing cell cycle arrest at the G0/G1 phase, supported by altered levels of cyclins D1 and D3 and CDK2. Impaired p-ERK/ERK signaling might be responsible for the delay in mitotic clonal expansion. These findings revealed that isopanduratin A is a strong adipogenic suppressor with multi-target mechanisms and contributes significantly to anti-obesogenic activity. These results suggest the potential of fingerroot as a functional food for weight control and obesity prevention.
ABSTRACT
Oxidative stress is a significant factor in the development of age-related macular degeneration (AMD), which results from cell damage, dysfunction, and death in the retinal pigmented epithelium (RPE). The use of natural compounds with antioxidant properties to protect RPE cells from oxidative stress has been explored in Dendrobium, a genus of orchid plants belonging to the family Orchidaceae. Two new compounds and seven known compounds from the MeOH extract of the whole plant of Dendrobium virgineum were successfully isolated and structurally characterized. Out of all the compounds isolated, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol (3) showed the highest protective effect against hydrogen peroxide (H2O2)-induced oxidative stress in human retinal pigment epithelial (ARPE-19) cells. Therefore, it was selected to evaluate its protective effect and mechanism on oxidative-stress-induced ARPE-19 cells. Cells were pre-treated with compound 3 at 25, 50, and 100 µg/mL for 24 h and then induced with 400 µM H2O2 for 1 h. The results demonstrated that compound 3 significantly (p < 0.05) increased cell viability by 10-35%, decreased ROS production by 10-30%, and reduced phosphorylation of p38, ERK1/2, and SAPK/JNK by 20-70% in a dose-dependent manner without toxicity. Furthermore, compound 3 significantly (p < 0.05) modulated the expression of apoptosis pathway proteins (cytochrome c, Bax and Bcl-2) by 20-80%, and enhanced SOD, CAT, and GPX activities, and GSH levels in a dose-dependent manner. These results suggest that compound 3 protects ARPE-19 cells against oxidative stress through MAPKs and apoptosis pathways, including the antioxidant system. Thus, compound 3 could be considered as an antioxidant agent for preventing AMD development by protecting RPE cells from oxidative stress and maintaining the retina. These findings open up new possibilities for the use of natural compounds in the treatment of AMD and other oxidative-stress-related conditions.
ABSTRACT
Lung cancer metastasis is a multifaceted process that accounts for 90% of cancer deaths. According to several studies, the epithelial-mesenchymal transition (EMT) plays an essential role in lung cancer metastasis. Therefore, this study aimed to investigate the potential pharmacological effect of cycloartocarpin on the suppression of metastasis-related behaviors and EMT. An MTT assay was used to examine cell viability. Cell migration was determined using a wound healing assay. Anchorage-independent cell growth was also performed. Western blot analysis was used to identify the key signaling proteins involved in the regulation of EMT and migration. The results found that non-toxic concentrations of cycloartocarpin (10-20 µM) effectively suppressed cell migration and attenuated anchorage-independent growth in H292, A549, and H460 cells. Interestingly, these effects were consistent with the findings of Western blot analysis, which revealed that the level of phosphorylated focal adhesion kinase (p-FAK), phosphorylated ATP-dependent tyrosine kinase (p-AKT), and cell division cycle 42 (Cdc42) were significantly reduced, resulting in the inhibition of the EMT process, as evidenced by decreased N-cadherin, vimentin, and slug expression. Taken together, the results suggest that cycloartocarpin inhibits EMT by suppressing the FAK/AKT signaling pathway, which is involved in Cdc42 attenuation. Our findings demonstrated that cycloartocarpin has antimetastatic potential for further research and development in lung cancer therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Epithelial-Mesenchymal Transition , Lung Neoplasms/metabolism , Cell Line, Tumor , Cell Movement , Signal TransductionABSTRACT
The most prevalent lung cancer is non-small cell lung cancer (NSCLC). This lung cancer type often develops other organ-specific metastases that are critical burdens in the treatment process. Orchid species in the genus Vanda have shown their potential in folkloric medication of diverse diseases but not all its species have been investigated, and little is known about their anticancer activities against NSCLC. Here, we firstly profiled the specialized metabolites of Vanda bensonii and examined their capability to inhibit growth and metastasis of NSCLC using NCI-H460 cells as a study model. Four phytochemicals, including phloretic acid methyl ester (1), cymbinodin-A (2), ephemeranthoquinone B (3), and protocatechuic acid (4), were isolated from the whole plant methanolic extract of V. bensonii. The most distinguished cytotoxic effect on NCI-H460 cells was observed in the treatments with crude methanolic extract and compound 2 with the half maximal inhibitory concentrations of 40.39 µg mL−1 and 50.82 µM, respectively. At non-cytotoxic doses (10 µg mL−1 or 10 µM), only compound 1 could significantly limit NCI-H460 cell proliferation when treated for 48 h, while others excluding compound 4 showed significant reduction in cell proliferation after treating for 72 h. Compound 1 also significantly decreased the migration rate of NCI-H460 cells examined through a wound-healing assay. Additionally, the crude extract and compound 1 strongly affected survival and growth of NCI-H460 cells under anchorage-independent conditions. Our findings proved that natural products from V. bensonii could be promising candidates for the future pharmacotherapy of NSCLC.
Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic useABSTRACT
Obesity is a critical factor for chronic metabolic syndromes. The culinary plant fingerroot (Boesenbergia rotunda) has been reported for its anti-obesity activity. The anti-adipogenic effects of pandurantin A, a main component of fingerroot cultivated in Indonesia, have been studied. Nevertheless, the suppressive effect and related mechanisms of pinostrobin, a major constituent of Thai fingerroot, on adipogenesis have never been thoroughly investigated. This study aimed to evaluate the potential of pinostrobin to inhibit adipocyte differentiation. Culturing pre-adipocytes from both mouse (3T3-L1) and human (PCS-210-010) with pinostrobin at non-toxic concentrations (5-20 µM) for 48 h obviously hindered their differentiation into mature adipocyte as evidenced by reduced cellular lipid droplets. The lower levels of lipid metabolism-mediating proteins, namely C/EBPα, PPARγ, and SREBP-1c, as well as cellular triglyceride content were demonstrated in pinostrobin-treated 3T3-L1 cells when compared to the untreated control group. Additionally, pinostrobin modulated the signals of MAPK (p38 and JNK) and Akt (Akt/GSK3ß, Akt/AMPKα-ACC). These findings suggest the benefit of fingerroot as a source of phytopharmaceuticals for obesity prevention and management, with pinostrobin as the active principle.
ABSTRACT
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 â²10 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.