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1.
Front Pharmacol ; 15: 1382787, 2024.
Article in English | MEDLINE | ID: mdl-38659592

ABSTRACT

Background: Prostate cancer and non-small cell lung cancer (NSCLC) present significant challenges in the development of effective therapeutic strategies. Hormone therapies for prostate cancer target androgen receptors and prostate-specific antigen markers. However, treatment options for prostatic small-cell neuroendocrine carcinoma are limited. NSCLC, on the other hand, is primarily treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors but exhibits resistance. This study explored a novel therapeutic approach by investigating the potential anticancer properties of vitekwangin B, a natural compound derived from Vitex trifolia. Methods: Vitekwangin B was chromatographically isolated from the fruits of V. trifolia. ANO1 protein levels in prostate cancer and NSCLC cells were verified and evaluated again after vitekwangin B treatment. Results: Vitekwangin B did not inhibit anoctamin1 (ANO1) channel function but significantly reduced ANO1 protein levels. These results demonstrate that vitekwangin B effectively inhibited cancer cell viability and induced apoptosis in prostate cancer and NSCLC cells. Moreover, it exhibited minimal toxicity to liver cells and did not affect hERG channel activity, making it a promising candidate for further development as an anticancer drug. Conclusion: Vitekwangin B may offer a new direction for cancer therapy by targeting ANO1 protein, potentially improving treatment outcomes in patients with prostate cancer and NSCLC. Further research is needed to explore its full potential and overcome existing drug resistance challenges.

2.
Environ Res ; 242: 117600, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37939806

ABSTRACT

Dichlorvos (2,2-Dichlorovinyl dimethyl phosphate, [DDVP]) belongs to the class of organophosphates and is widely used as an insecticide in agriculture farming and post-harvest storage units. Extensive research has been conducted to assess the factors responsible for the presence of DDVP in terrestrial and aquatic ecosystems, as well as the entire food chain. Numerous studies have demonstrated the presence of DDVP metabolites in the food chain and their toxicity to mammals. These studies emphasize that both immediate and chronic exposure to DDVP can disrupt the host's homeostasis, leading to multi-organ damage. Furthermore, as a potent carcinogen, DDVP can harm aquatic systems. Therefore, understanding the contamination of DDVP and its toxicological effects on both plants and mammals is vital for minimizing potential risks and enhancing safety in the future. This review aimed to comprehensively consolidate information about the distribution, ecological effects, and health impacts of DDVP, as well as its metabolism, detection, prevention, and remediation strategies. In summary, this study observes the distribution of DDVP contaminations in vegetables and fruits, resulting in significant toxicity to humans. Although several detection and bioremediation strategies are emerging, the improper application of DDVP and the alarming level of DDVP contamination in foods lead to human toxicity that requires attention.


Subject(s)
Dichlorvos , Insecticides , Organophosphorus Compounds , Animals , Humans , Dichlorvos/toxicity , Dichlorvos/metabolism , Ecosystem , Insecticides/toxicity , Mammals/metabolism
3.
J Diet Suppl ; 21(3): 389-407, 2024.
Article in English | MEDLINE | ID: mdl-38062982

ABSTRACT

Senescence can promote hyperplastic pathologies, such as cancer. Prostate cancer is the second most common type of cancer in men. The p21-mediate cellular senescence, facilitated through the tumor suppressor p53-dependent pathway, is considered the primary mechanism for cancer treatment. Aloe-emodin, has been reported to exert anticancer effects in various types of cancers. This study aimed to investigate the bioactivity of aloe-emodin in LNCaP cells via the activation of p21-mediated cellular senescence. Aloe-emodin treatment increased the percentage of cells in the G1 phase while decreasing the percentage in the S phase. This effect was reflected in the expression levels of proteins associated with cell cycle progression, such as p21CIP, retinoblastoma protein, and cyclin-dependent kinase2/4 in LNCaP cells. However, aloe-emodin-treated LNCaP cells did not induce cell cycle arrest at G2/M checkpoint. Moreover, increased senescence-associated-galactosidase activity was observed in a dose-dependent manner following treatment with aloe-emodin. Aloe-emodin also induced DNA damage by modulating the expression of histone H2AX and lamin B1. Furthermore, aloe-emodin inhibited the proliferation of LNCaP cells, contrasting with the exponential growth observed in the nontreated cells. Importantly, this inhibition did not impact the immune system, as evidenced by the increased proliferation of splenocytes isolated from mice. These findings provide preliminary evidence of the anticancer effect of aloe-emodin in LNCaP cells, necessitating further investigations into the underlying mechanisms in vivo and human subjects.


Subject(s)
Aloe , Anthraquinones , Emodin , Prostatic Neoplasms , Rheum , Humans , Mice , Animals , Male , Emodin/pharmacology , Apoptosis , Cell Cycle , Cellular Senescence , Prostatic Neoplasms/drug therapy , Cell Line, Tumor
4.
Food Chem ; 439: 138086, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38043281

ABSTRACT

Dehulled hempseed (DHS), fermented dehulled hempseed (FDHS), hempseed cake (HSC), and fermented HSC (FHSC) were examined for their phytochemical composition, health benefits, and rheological characteristics. At 500 µg/mL concentration, DHS, FDHS, HSC, and FHSC extracts exhibited the ability to inhibit DPPH radicals, with 32.46 %, 47.35 %, 33.85 %, and 47.41 %, respectively. Similarly, they demonstrated potential to scavenge ABTS radicals by 13.7 %, 27.87 %, 14.40 % and 25.70 %, respectively. For lipase inhibition activity, FDHS (72.92 %) and FDHS (85.89 %) outperformed DHS (52.94 %) and HSC (43.08 %). Furthermore, FHSC enhanced the survival and reduced fat accumulation in glucose-supplemented Caenorhabditis elegans. We used HPLC and UHPLC-ESI-QTOF-MS for metabolite analysis, quantifying eight polyphenols using HPLC and identifying thirty-four metabolites with UHPLC-ESI-QTOF-MS. Generally, metabolomics indicated an improved metabolite profile after fermentation. Fermentation also showed impact on rheological characteristics, modifying viscosity, loss modulus, and storage modulus. These findings collectively demonstrate the ability of fermentation in enhancing overall value of hempseed.


Subject(s)
Antioxidants , Polyphenols , Fermentation , Polyphenols/chemistry , Antioxidants/chemistry , Glucose , Plant Extracts/chemistry
5.
Environ Res ; 246: 118004, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38145732

ABSTRACT

The colonization of pathogenic microbes poses a significant clinical barrier that hinders the physiological wound-healing process. Addressing this challenge, we developed a novel wound dressing using a modified cotton gauze dressing coated with fucoidan and functionalized with silver nanoparticles (LB-Ag NPs-FN-OCG) for the rapid treatment of infected wounds. Firstly, phytochemical-capped LB-Ag NPs were synthesized and characterized using high performance liquid chromatography (HPLC), transmission electron microscopy (TEM), and zeta potential analysis. Secondly, different concentrations of LB-Ag NPs (0.1%-1%) were functionalized into FN-OCG to identify appropriate concentrations that were non-toxic with superior antibacterial activities. Screening assays, including antibacterial, hemolysis, chick chorioallantoic membrane (CAM) assay, and cytotoxicity assay, revealed that LB-Ag NPs (0.5%)-FN-OCG were non-toxic and demonstrated greater efficiency in inhibiting bacterial pathogens (Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes) and promoting fibroblast cell (NIH3T3) migration. In vivo assays revealed that LB-Ag NPs (0.5%)-FN-OCG treatment exhibited excellent wound healing activity (99.73 ± 0.01%) compared to other treatments by inhibiting bacterial colonization, maintaining the blood parameters, developing granulation tissue, new blood vessels, and collagen deposition. Overall, this study highlights that LB-Ag NPs (0.5%)-FN-OCG serve as a antibacterial wound dressing for infected wound healing applications.


Subject(s)
Metal Nanoparticles , Polysaccharides , Silver , Mice , Animals , Silver/chemistry , Metal Nanoparticles/chemistry , NIH 3T3 Cells , Wound Healing , Anti-Bacterial Agents/pharmacology , Bandages
6.
Sci Rep ; 13(1): 20570, 2023 11 23.
Article in English | MEDLINE | ID: mdl-37996535

ABSTRACT

Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p < 0.001) and 57% (p < 0.05), respectively, which have more than 2- and 1.5-fold stronger effects compared to the control. Furthermore, both increased the expression level of proteins involved in the PI3K-Akt-mTOR signaling pathway and myogenic proteins, including myogenin and MyoD. This study demonstrated that moracin E and M exhibit cell proliferative effects on skeletal muscle cells through the PI3K-Akt-mTOR signaling pathway.


Subject(s)
Morus , Proto-Oncogene Proteins c-akt , Cell Proliferation , Morus/chemistry , Muscle, Skeletal/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
7.
Chem Biodivers ; 20(11): e202301296, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37842907

ABSTRACT

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).


Subject(s)
Anti-Infective Agents , Antineoplastic Agents , Vitex , Humans , Iridoids/chemistry , Vitex/chemistry , Fruit/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/analysis , Plant Extracts/analysis
8.
Food Chem ; 428: 136722, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37429240

ABSTRACT

The impact of fermentation and germination on the metabolite profile and bioactive of 'Cheongsam' hempseed was investigated. The seeds were germinated for 3 days at 26 °C and fermented for 48 h at 37 °C using Pediococcus acidilactici (SRCM201591). The raw (R), fermented seed (RF), sprouts (S), and fermented sprouts (SF) extracts were assessed for anti-nutrients, metabolite profile, and selected bioactivities. Germination and fermentation significantly altered anti-nutrient levels (tannins, saponins, phytic acid, and trypsin inhibitors). They increased total polyphenols, flavonoid contents, and individual polyphenols and cannabinoids. SF demonstrated the highest ABTS (IC50, 291.65 µg/mL) and DPPH (IC50, 345.30 µg/mL) scavenging capacities. However, S (IC50, 73.295 µg/mL) was the most potent anti-inflammatory ingredient. SF (IC50, 74.07 µg/mL) exhibited the most potent alpha-glucosidase inhibition for enzyme inhibitions, while RF (IC50, 63.31 µg/mL) showed the best lipase inhibition potential. The findings demonstrate that germination and fermentation could improve the functional properties of hempseed.


Subject(s)
Cannabis , Lactobacillales , Antioxidants/chemistry , Fermentation , Cannabis/chemistry , Lactobacillales/metabolism , Polyphenols/analysis , Seeds/chemistry , Germination
9.
Front Pharmacol ; 14: 1163970, 2023.
Article in English | MEDLINE | ID: mdl-37274097

ABSTRACT

Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from Schisandra sphenanthera, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent.

10.
Environ Sci Pollut Res Int ; 30(21): 60976-60993, 2023 May.
Article in English | MEDLINE | ID: mdl-37042914

ABSTRACT

In the recent past, phytomolecules are exponentially applied in discovering the antidiabetic drug due to less adverse effects. This work screened the active solvent fraction of Lespedeza cuneata based on the phytochemical, enzyme inhibition, and antioxidant properties. The antioxidant efficacy of the different fractions of the L. cuneata was assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing power, hydrogen peroxide, and hydroxyl radical scavenging assays. The digestive enzyme (α-amylase and α-glucosidase) inhibitory activity was also evaluated. The phytochemical composition of ethyl acetate fraction of L. cuneata (Lc-EAF) was studied by UHPLC-QTOF-MS/MS. The effect of Lc-EAF treatments on glucose uptake was studied in insulin resistance HepG2 cells (IR-HepG2). Further, the antidiabetic effect of Lc-EAF in streptozotocin (STZ)-induced diabetic mice were demonstrated. Ethyl acetate, hexane, and methanol fractions of the L. cuneata showed notable antioxidant, α-amylase, and α-glucosidase inhibitory properties. Among the fractions, Lc-EAF was found to be the most potent. The Lc-EAF exhibited an IC50 of 205.32 ± 23.47 µg/mL and 105.32 ± 13.93 µg/mL for α-amylase and α-glucosidase inhibition, respectively. In addition, 75 µg/mL of Lc-EAF exposure enhanced glucose uptake (68.23%) in IR-HepG2 cells. In vivo study indicated that treatment of Lc-EAF (100 mg/kg b.wt) maintained the blood glucose level through reduced insulin level while improving the lipid profile, hepatic, and renal markers. These findings suggest that Lc-EAF could be considered a prominent source for antidiabetic, anti-hyperlipidemic, and anti-ROS potentials.


Subject(s)
Diabetes Mellitus, Experimental , Lespedeza , Rats , Mice , Animals , Hypoglycemic Agents/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Diabetes Mellitus, Experimental/drug therapy , Streptozocin , alpha-Glucosidases , Tandem Mass Spectrometry , Plant Extracts/chemistry , alpha-Amylases , Phytochemicals/pharmacology , Phytochemicals/chemistry , Glucose
11.
Plants (Basel) ; 12(5)2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36903879

ABSTRACT

Castanea crenata (Fagaceae) is a species of chestnut tree that is endemic to the Republic of Korea and Japan. While its kernels are consumed, chestnut by-products such as shells and burs, which account for 10-15% of the total weight, are discarded as waste. Phytochemical and biological studies have been carried out to eliminate this waste and develop high-value products from its by-products. In this study, five new compounds (1-2, 6-8) along with seven known compounds were isolated from the shell of C. crenata. This is the first study to report diterpenes from the shell of C. crenata. Comprehensive spectroscopic data including 1D, 2D NMR, and CD spectroscopy were used to determine the compound structures. All isolated compounds were examined for their ability to stimulate dermal papilla cell proliferation using a CCK-8 assay. In particular, 6ß,7ß,16α,17-Tetrahydroxy-ent-kauranoic acid, isopentyl-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranoside, and ellagic acid exhibited the most potent proliferation activity of all.

12.
Appl Biochem Biotechnol ; 195(6): 3822-3839, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36260249

ABSTRACT

In this study, two extracellular polysaccharides (TEPS1 and TEPS2) were isolated from the endophytic fungus (Talaromyces purpureogenus) and purified by DEAE-Sepharose Fast Flow column using NaCl as gradient eluent. The HPLC analysis displayed that TEPS1 was composed of mannose (38.70%), ribose (25.02%), glucose (19.34%), and galactose (16.94%) while the TEPS2 composed by mannose (100%). The NMR results indicated that TEPS1 exhibited α-glycosidic configurations. The both polysaccharides, TEPS1 and TEPS2 were exhibited a good antioxidant activity in terms of DPPH, ABTS, and •OH scavenging. However, TEPS1 showed a higher antioxidant activity than TEPS2. The IC50 of TEPS1 were 32.16, 192.57, and 54.67 µg·mL-1, for DPPH, ABTS, and •OH radical scavenging, respectively. Furthermore, TEPS1 showed the high cellular antioxidant and wound healing activity in the human embryonic kidney (HEK293) cell line. Overall, these two polysaccharides were promising in antioxidant activity.


Subject(s)
Antioxidants , Talaromyces , Humans , Antioxidants/chemistry , Mannose , HEK293 Cells , Talaromyces/metabolism , Polysaccharides/chemistry , Wound Healing
13.
J Ethnopharmacol ; 302(Pt A): 115940, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36384207

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Echinosophora koreensis Nakai is an endemic plant species distributed in a limited area within the Korean province of Gangwon, including the Yanggu-gun, Inje-gun, Cheorwon-gun, Chuncheon-si, and Hongcheon-gun counties. It is used in traditional medicine to treat various disorders, such as fever, skin diseases, diuresis, and neuralgia. MATERIALS AND METHODS: This study demonstrated the effects of E. koreensis Nakai root extract (EKRE) on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Cell viability was assessed through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nitric oxide (NO) production was measured using Griess reagent. Interleukin (IL)-6 and tumor necrosis factor (TNF) levels were assessed using enzyme-linked immunosorbent assays. Inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinase (MAPK) expression were assessed using Western blot analysis. To examine the effects of EKRE in vivo, it was administered orally at doses of 50 or 200 mg/kg for 3 days in mice. Edema in the paws was induced through λ-carrageenan injection and measured hourly for up to 5 h using calipers. RESULTS: EKRE markedly suppressed LPS-generated NO, IL-6, and iNOS production in RAW 264.7 cells. Moreover, it suppressed the activation of the NF-κB and MAPK in LPS-stimulated cells. Furthermore, EKRE significantly inhibited carrageenan-induced edema in mouse paws. There were no significant differences in IL-6 and TNF production in paw tissue harvested from mice, but levels decreased at high EKRE concentrations (200 mg/kg). CONCLUSION: The results of this study provided validation for EKRE-induced inhibition of inflammatory responses in vitro and in vivo. This research suggested that EKRE is a promising treatment for inflammatory disorders.


Subject(s)
Anti-Inflammatory Agents , Fabaceae , Plant Extracts , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Carrageenan , Disease Models, Animal , Edema/chemically induced , Edema/drug therapy , Fabaceae/chemistry , Interleukin-6 , Lipopolysaccharides , Mitogen-Activated Protein Kinases , NF-kappa B , Nitric Oxide , Plant Extracts/pharmacology , RAW 264.7 Cells
14.
Nat Prod Res ; 37(6): 863-870, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35787219

ABSTRACT

Three new monoterpenoid glycosides (1-3) and one new flavanol (4) along with 15 known compounds were isolated from the twig of Hamamelis japonica Sieb. et Zucc. The chemical constituent study of the twig of H. japonica has performed for the first time in the present investigation. Their structures were determined based on extensive spectroscopic methods including 1 D and 2 D NMR and CD spectra data. All isolated compounds were tested for their antiviral activities against HRV1B-, EV71-, PR8- and CVB3-infected Vero cells. Among the tested compounds, (-)-epigallocatechin 3-O-gallate exhibited the most consistent and effective antiviral activities against EV71 and PR8 infections.


Subject(s)
Antiviral Agents , Hamamelis , Animals , Chlorocebus aethiops , Antiviral Agents/chemistry , Vero Cells , Glycosides/chemistry , Magnetic Resonance Spectroscopy
15.
J Asian Nat Prod Res ; 25(1): 18-26, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35306942

ABSTRACT

Three new chromanes, malloapeltas J-L (1-3), and one new flavone C-glycoside, malloflavoside (4), together with four known compounds, apigenin 6-C-ß-D-xylopyranosyl-8-C-α-L-arabinopyranoside (5), apigenin 6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (6), apigenin 7-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (7), and acantrifoside E (8) were isolated from the methanol extract of the leaves of Mallotus apelta. Their chemical structures were determined using spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS methods. All the isolated compounds were evaluated their cytotoxic activity against human prostate cancer (PC-3) and human breast cancer (MCF-7) cells, but none of them showed cytotoxicities on both human cancer cell lines.


Subject(s)
Flavones , Mallotus Plant , Humans , Apigenin , Glycosides/pharmacology , Glycosides/chemistry , Flavones/pharmacology
16.
Int J Biol Macromol ; 222(Pt B): 2744-2760, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36243158

ABSTRACT

Hyaluronic acid (HA) plays a vital role in cellular processes and its contribution to physical and immunological barriers is considered to be an important property for the formulation of modern therapeutics. With the increasing demand for non-toxic and targeted therapy, HA-based materials could be utilized for biomedical applications due to their tendency to bio-mimic the hosts. Moreover, HA is a versatile compound in the fabrication of HA-based products such as hydrogels, nanofibers, and 3D materials. These have been implemented in various medical fields, such as bone and tissue regeneration, topical gels for wound healing, and cancer treatment via HA-loaded drug delivery approaches. Herein, we have discussed the characteristics of HA and its significance in drug delivery in addition to synergistic effects with other therapeutic compounds in the fields of nanomedicine, tissue engineering, and regenerative medicine.


Subject(s)
Regenerative Medicine , Tissue Engineering , Hyaluronic Acid/therapeutic use , Nanomedicine , Hydrogels/therapeutic use
17.
Nat Prod Res ; : 1-7, 2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36239487

ABSTRACT

Using combined chromatographic methods, two new triterpenoid glycosides, bacopasaponin K (1) and bacopasaponin L (2), along with eight known compounds, bacopaside IV (3), bacopaside VII (4), bacopasaponin E (5), bacoside A3 (6), bacopasaponin F (7), bacopasaponin C (8), bacopaside I (9), and bacopaside II (10) were isolated from the methanol extract of the Bacopa monnieri. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS and comparing with the NMR data reported in the literature. All these compounds were evaluated for their cytotoxic activity using the cell counting kit-8 (CCK-8) assay. Compounds 4, 6, 8, and 10 exhibited potential cytotoxic effects against human lung cancer cells (PC9) and human colon cancer cells (SW620).

18.
Molecules ; 27(17)2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36080161

ABSTRACT

Growth and maintenance of skeletal muscle is essential for athletic performance and a healthy life. Stimulating the proliferation and differentiation of muscle cells may help prevent loss of muscle mass. To discover effective natural substances enabling to mitigate muscle loss without side effects, we evaluated muscle growth with several compounds extracted from Catalpa bignonioides Walt. Among these compounds, pinoresinol and vanillic acid increased C2C12, a mouse myoblast cell line, proliferation being the most without cytotoxicity. These substances activated the Akt/mammalian target of the rapamycin (mTOR) pathway, which positively regulates the proliferation of muscle cells. In addition, the results of in silico molecular docking study showed that they may bind to the active site of insulin-like growth factor 1 receptor (IGF-1R), which is an upstream of the Akt/mTOR pathway, indicating that both pinoresinol and vanillic acid stimulate myoblast proliferation through direct interaction with IGF-1R. These results suggest that pinoresinol and vanillic acid may be a natural supplement to improve the proliferation of skeletal muscle via IGF-1R/Akt/mTOR signaling and thus strengthen muscles.


Subject(s)
Proto-Oncogene Proteins c-akt , Vanillic Acid , Animals , Cell Proliferation , Furans , Insulin-Like Growth Factor I/metabolism , Lignans , Mammals/metabolism , Mice , Molecular Docking Simulation , Muscle, Skeletal/metabolism , Myoblasts/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Vanillic Acid/metabolism , Vanillic Acid/pharmacology
19.
Biomed Pharmacother ; 153: 113373, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35785700

ABSTRACT

Anoctamin 1 (ANO1) is a calcium-activated chloride channel found in various cell types and is overexpressed in non-small cell lung cancer (NSCLC), a major cause of cancer-related mortality. With the rising interest in development of druggable compounds for NSCLC, there has been a corresponding rise in interest in ANO1, a novel drug target for NSCLC. However, as ANO1 inhibitors that have been discovered simultaneously exhibit both the functions of an inhibition of ANO1 channel as well as a reduction of ANO1 protein levels, it is unclear which of the two functions directly causes the anticancer effect. In this study, verteporfin, a chemical compound that reduces ANO1 protein levels was identified through high-throughput screening. Verteporfin did not inhibit ANO1-induced chloride secretion but reduced ANO1 protein levels in a dose-dependent manner with an IC50 value of ~300 nM. Moreover, verteporfin inhibited neither P2Y receptor-induced intracellular Ca2+ mobilization nor cystic fibrosis transmembrane conductance regulator (CFTR) channel activity, and molecular docking studies revealed that verteporfin bound to specific sites of ANO1 protein. Confirming that verteporfin reduces ANO1 protein levels, we then investigated the molecular mechanisms involved in its effect on NSCLC cells. Interestingly, verteporfin decreased ANO1 protein levels, the EGFR-STAT3 pathway as well as ANO1 mRNA expression. Verteporfin reduced the viability of ANO1-expressing cells (PC9, and gefitinib-resistant PC9) and induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage. However, it did not affect hERG channel activity. These results show that the anticancer mechanism of verteporfin is caused via the down-regulation of ANO1.


Subject(s)
Anoctamin-1 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoplasm Proteins , Verteporfin , Anoctamin-1/genetics , Anoctamin-1/metabolism , Calcium/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Chloride Channels/metabolism , Down-Regulation , Humans , Lung Neoplasms/drug therapy , Molecular Docking Simulation , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Verteporfin/pharmacology
20.
Nat Prod Res ; 36(1): 142-149, 2022 Jan.
Article in English | MEDLINE | ID: mdl-32441150

ABSTRACT

Two new, aramatosides A and B (1 and 2), together with seven known oleanane-type triterpene saponins (3-9) were isolated from the leaves of Aralia armata. Their structures were determined by combination of HR-ESI-MS, 1 D and 2 D NMR spectral data as well as comparison with the previous literature. Compounds 6-9 exhibited cytotoxic effects towards three human cancer cell lines (HT29, A2058, and A549) with IC50 values ranging from 2.01 ± 0.17 to 18.8 ± 1.17 µM. Especially, compound 7 (narcissiflorin) showed significant cytotoxic activity against HT29 and A549 cell lines with IC50 values of 2.02 ± 1.65 and 2.01 ± 0.17 µM, respectively, which are smaller than those of positive control irinotecan hydrochloride (IC50 values of 10.3 ± 1.32 and 9.89 ± 0.19 µM).


Subject(s)
Antineoplastic Agents, Phytogenic , Aralia , Oleanolic Acid , Saponins , Triterpenes , Antineoplastic Agents, Phytogenic/pharmacology , Humans , Molecular Structure , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/pharmacology , Plant Leaves , Saponins/pharmacology , Triterpenes/pharmacology
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