Estrogenic activity of Derris scandens stem extracts and its major compounds using MCF-7 cell proliferation assay and estrogen-related gene expression.

Derris scandens, which contains isoflavones and prenylated derivatives, has analgesic and anti-inflammatory properties and is an ingredient in traditional Thai medicine for perimenopause and menopause. However, the estrogenic activity of D. scandens has not yet been explored. Therefore, this study aimed to examine the estrogenic activity of the stem extract of D. scandens and its isoflavone derivatives. In this study, we conducted a proliferation assay in MCF-7 cells and qRT-PCR to assess gene expression. We found that the relative cell proliferation of compounds (1 µM) was ranked in the following order as compared to 0.1 nM 17ß-estradiol (100%): genistein (97.84%) > derrisisoflavone A (83.17%) > genistein-7-O-[α-rhamnopyranosyl-(1→6)-glucopyranoside] (GTG) (69.55%) > 6,8-diprenylgenistein (51.91%) > lupalbigenin (18.72%). Furthermore, co-treatment with 1 µM lupalbigenin and 0.1 nM 17ß-estradiol was performed, which decreased cell proliferation to 80.38%. In vitro results suggest that lupalbigenin has an estrogen-antagonistic effect. At a dose of 1 µM, genistein had the strongest efficacy in increasing the expression of human estrogen receptor ß (ERß) by 4.0-fold compared to the control. Furthermore, GTG augmented the gene expression of human estrogen receptor α (ERα) and ERß by 1.5- and 3.4-fold, respectively. Prenylated derivatives of genistein (derrisisoflavone A, 6,8-diprenylgenistein, and lupalbigenin) significantly suppressed the gene expression of human androgen receptor (AR). The administration of crude extract at 10 µg/mL significantly suppressed AR (0.6-fold) and transmembrane protease serine 2 (0.1-fold) expression, but did not significantly affect ERα and ERß gene expression. This herbal medicine may be safe for estrogen-exposed breast cancer patients.

Identification of Major Bioactive Anti-inflammatory Compounds of Derris scandens Stem Using RAW 264.7 Cells and HPLC-UV Analysis.

Derris scandens (DS) is widely recognized for its therapeutic properties, specifically its analgesic effects, which significantly alleviate muscle pain. The chemical constituents of DS stem include various isoflavone derivatives. However, there is currently a lack of specified anti-inflammatory chemical markers and analytical methods for quality control. The present study aimed to evaluate the anti-inflammatory activity of DS and its constituents using the RAW 264.7 cell model. The expression of inflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and 5-lipoxygenase (5-LOX) was examined using quantitative RT-PCR. An high-performance liquid chromatography with a UV detection method was developed to quantitatively analyze genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-ß-glucopyranoside, genistein, derrisisoflavone A, lupalbigenin, and 6,8-diprenylgenistein in DS stem. The developed HPLC-UV method demonstrated high sensitivity with limits of detection and quantification ranging from 0.01 to 0.06 µg/mL and 0.03 to 0.18 µg/mL, respectively. The accuracy of the method ranged from 93.3 to 109.6%. Furthermore, the repeatability and reproducibility of the method were suitable, as indicated by the relative standard deviations of ≤ 3.02% and ≤ 6.22%, respectively. The DS extract notably inhibited NO production, exhibiting effects comparable to those of 500 µM diclofenac, and substantially suppressed the expression of iNOS, COX-2, IL-6, and 5-LOX of lipopolysaccharide (LPS)-induced genes. As to the pure isoflavone derivatives, the order of NO production inhibition was found to be genistein > lupalbigenin > derrisisoflavone A > 6,8-diprenylgenistein > genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-ß-glucopyranoside. Genistein, derrisisoflavone A, and 6,8-diprenylgenistein significantly suppressed the upregulation of all LPS-induced genes. Consequently, these compounds are recommended as anti-inflammatory markers for the quantitative chemical analysis of DS.

Multifunctional effect of flavonoids from Millettia brandisiana against Alzheimer's disease pathogenesis.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuronal death. Fifteen flavonoids from Millettia brandisiana were evaluated for the multifunctional effect against AD pathogenesis, including butyrylcholine esterase (BuChE) inhibition, anti-amyloid beta (Aß) aggregation and neuroprotection against hydrogen peroxide (H2O2) toxicity in differentiated human neuroblastoma SH-SY5Y cell. To understand the mechanism and structure-activity relationship, binding interactions between flavonoids and the BuChE and Aß were investigated in silico. Furthermore, drug-likeness properties and ADMET parameters were evaluated in silico using SwissADME and pKCSM tools. All flavonoids exhibit a good drug-likeness profile. Six flavonoids have potency in BuChE inhibition, and four flavonoids show potency in anti-Aß aggregation. Flavonoids with the 6″,6″-dimethylchromeno- [2″,3″:7,8]-flavone structure show a favorable multifunctional effect. In silico analysis showed that flavonoids can bind in various positions to the catalytic triad, anionic site, and acyl pocket. In Aß1-42, potential flavonoids can attach to the central hydrophobic region and the C terminal hydrophobic and interfere with Aß interchain hydrogen binding. When compared together, it can inhibit multifunctional action with a favorable ADMET parameter and drug-likeness profile. In addition, candidine can prevent neuronal damage in differentiated SH-SY5Y neuroblastoma cells induced by H2O2 in a dose-dependent manner.

The Effect of Ethanol Extract from Mesua ferrea Linn Flower on Alzheimer's Disease and Its Underlying Mechanism.

The effects of Mesua ferrea Linn flower (MFE) extract on the pathogenic cascade of Alzheimer's disease (AD) were determined by an in vitro and cell culture model in the search for a potential candidate for the treatment of AD. The 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay exhibited that the MFE extract had antioxidant activities. According to the Ellman and the thioflavin T method's result, the extracts could inhibit acetylcholinesterase and ß-amyloid (Aß) aggregation. Studies on neuroprotection in cell culture found that the MFE extract could reduce the death of human neuroblastoma cells (SH-SY5Y) caused by H2O2 and Aß. Western blot analysis exhibited that the MFE extract alleviated H2O2-induced neuronal cell damage by downregulating the pro-apoptotic proteins, including cleaved caspase-3, Bax, and by enhancing the expression of anti-apoptotic markers including MCl1, BClxl, and survivin. Moreover, MFE extract inhibited the expression of APP, presenilin 1, and BACE, and increased the expression of neprilysin. In addition, the MFE extract could enhance scopolamine-induced memory deficit in mice. Overall, results showed that the MFE extract had several modes of action related to the AD pathogenesis cascade, including antioxidants, anti-acetylcholinesterase, anti-Aß aggregation, and neuroprotection against oxidative stress and Aß. Therefore, the M. ferrea L. flower might be a possibility for further development as a medication for AD.

Anti-inflammatory effects of Derris scandens extract on narrowband-ultraviolet B exposed HaCaT human keratinocytes.

Narrowband-ultraviolet B (NB-UVB) has been used to treat skin diseases such as psoriasis. Chronic use of NB-UVB might cause skin inflammation and lead to skin cancer. In Thailand, Derris Scandens (Roxb.) Benth. is used as an alternative medicine to nonsteroidal anti-inflammatory drugs (NSAIDs) for low back pain and osteoarthritis. Therefore, this study aimed to evaluate the potential anti-inflammatory effect of Derris scandens extract (DSE) on pre- and post exposed NB-UVB human keratinocytes (HaCaT). The results indicated that DSE could not protect HaCaT from cell morphology changes or DNA fragmentation and could not recover cell proliferation ability from the NB-UVB effects. DSE treatment reduced the expression of genes related to inflammation, collagen degradation, and carcinogenesis, such as IL-1α, IL-1ß, IL-6, iNOS, COX-2, MMP-1, MMP-9, and Bax. These results indicated the potential use of DSE as a topical preparation against NB-UVB-induced inflammation, anti-aging, and prevention of skin cancer from phototherapy.

Unveiling the Potent Antiviral and Antioxidant Activities of an Aqueous Extract from Caesalpinia mimosoides Lamk: Cheminformatics and Molecular Docking Approaches.

Our group previously demonstrated that Caesalpinia mimosoides Lamk exhibits many profound biological properties, including anticancer, antibacterial, and antioxidant activities. However, its antiviral activity has not yet been investigated. Here, the aqueous extract of C. mimosoides was prepared from the aerial parts (leaves, stalks, and trunks) to see whether it exerts anti-influenza (H1N1) effects and to reduce the organic solvents consumed during extraction, making it a desirable approach for the large-scale production for medical uses. Our plant extract was quantified to contain 7 g of gallic acid (GA) per 100 g of a dry sample, as determined using HPLC analysis. It also exerts potent antioxidant activities comparable to those of authentic GA. According to untargeted metabolomics (UPLC-ESI(-)-QTOF-MS/MS) with the aid of cheminformatics tools (MetFrag (version 2.1), SIRIUS (version 5.8.3), CSI:FingerID (version 4.8), and CANOPUS), the major metabolite was best annotated as "gallic acid", phenolics (e.g., quinic acid, shikimic acid, and protocatechuic acid), sugar derivatives, and dicarboxylic acids were deduced from this plant species for the first time. The aqueous plant extract efficiently inhibited an influenza A (H1N1) virus infection of MDCK cells with an IC50 of 5.14 µg/mL. Of equal importance, hemolytic activity was absent for this plant extract, signifying its applicability as a safe antiviral agent. Molecular docking suggested that GA interacts with conserved residues (e.g., Arg152 and Asp151) located in the catalytic inner shell of the viral neuraminidase (NA), sharing the same pocket as those of anti-neuraminidase drugs, such as laninamivir and oseltamivir. Additionally, other metabolites were also found to potentially interact with the active site and the hydrophobic 430-cavity of the viral surface protein, suggesting a possibly synergistic effect of various phytochemicals. Therefore, the C. mimosoides aqueous extract may be a good candidate for coping with increasing influenza virus resistance to existing antivirals.

The Potential of Purple Waxy Corn Cob (Zea mays L.) Extract Loaded-Sericin Hydrogel for Anti-Hyperpigmentation, UV Protection and Anti-Aging Properties as Topical Product Applications.

Sericin-hydrogel formulations incorporating purple waxy corn (Zea mays L.) cob extract (PWCC) were developed as potential topical skin cosmetic products. Sericin has wound healing properties, protects against ultraviolet (UV) radiation, and exhibits anti-inflammatory, anti-oxidation, and anti-tyrosinase activities. PWCC is a rich source of anthocyanins with antioxidants, UV protective, anti-inflammatory, and collagen-enhancing activities. Six hydrogel formulations (S1-S6) were investigated for anti-melanogenesis on the B16F10 melanoma cell line and UV-protection on human keratinocytes (HaCaT) and anti-aging activities on normal human dermal fibroblasts (NHDFs). The results showed that the hydrogel formulations enhanced the anthocyanin permeation through the skin. The S4 formulation indicated the highest inhibition of tyrosinase activity and reduced the melanin pigment, increased the cell viability of the UV-induced HaCaT cells, the inhibition of collagenase and elastase, and increased the collagen type I production without cytotoxicity. Therefore, the PWCC loaded-sericin hydrogels show a high potential as a novel anti-hyperpigmentation, UV protection, and anti-aging products for topical applications.

Synthesis of Ferulenol by Engineered Escherichia coli: Structural Elucidation by Using the In Silico Tools.

4-Hydroxycoumarin (4HC) has been used as a lead compound for the chemical synthesis of various bioactive substances and drugs. Its prenylated derivatives exhibit potent antibacterial, antitubercular, anticoagulant, and anti-cancer activities. In doing this, E. coli BL21(DE3)pLysS strain was engineered as the in vivo prenylation system to produce the farnesyl derivatives of 4HC by coexpressing the genes encoding Aspergillus terreus aromatic prenyltransferase (AtaPT) and truncated 1-deoxy-D-xylose 5-phosphate synthase of Croton stellatopilosus (CstDXS), where 4HC was the fed precursor. Based on the high-resolution LC-ESI(±)-QTOF-MS/MS with the use of in silico tools (e.g., MetFrag, SIRIUS (version 4.8.2), CSI:FingerID, and CANOPUS), the first major prenylated product (named compound-1) was detected and ultimately elucidated as ferulenol, in which information concerning the correct molecular formula, chemical structure, substructures, and classifications were obtained. The prenylated product (named compound-2) was also detected as the minor product, where this structure proposed to be the isomeric structure of ferulenol formed via the tautomerization. Note that both products were secreted into the culture medium of the recombinant E. coli and could be produced without the external supply of prenyl precursors. The results suggested the potential use of this engineered pathway for synthesizing the farnesylated-4HC derivatives, especially ferulenol.