Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were determined by the interpretation of spectroscopic methods, especially NMR technologies (COSY, HSQC, HMBC, and NOESY). In addition, a convenient method for concentrating the alkylamide-rich fraction and analyzing fingerprint profile of A. oleracea was established.

The Aquilaria malaccensis (Thymelaeaceae) tree is a source of precious fragrant resin, called agarwood, which is widely used in traditional medicines in East Asia against diseases such as asthma. In our continuous search for active natural products, A. malaccensis seeds ethanolic extract demonstrated antiallergic effect with an IC₅₀ value less than 1 µg/mL. Therefore, the present research aimed to purify and identify the antiallergic principle of A. malaccensis through a bioactivity-guided fractionation approach. We found that phorbol ester-rich fraction was responsible for the antiallergic activity of A. malaccensis seeds. One new active phorbol ester, 12-O-(2Z,4E,6E)-tetradeca-2,4,6-trienoylphorbol-13-acetate, aquimavitalin (1) was isolated. The structure of 1 was assigned by means of 1D and 2D NMR data and high-resolution mass spectrometry (HR-MS). Aquimavitalin (1) showed strong inhibitory activity in A23187- and antigen-induced degranulation assay with IC₅₀ values of 1.7 and 11 nM, respectively, with a therapeutic index up to 71,000. The antiallergic activities of A. malaccensis seeds and aquimavitalin (1) have never been revealed before. The results indicated that A. malaccensis seeds and the pure compound have the potential for use in the treatment of allergy.

Plant type III polyketide synthases produce diverse bioactive molecules with a great medicinal significance to human diseases. Here, we demonstrated versatility of a stilbene synthase (STS) from Pinus Sylvestris, which can accept various non-physiological substrates to form unnatural polyketide products. Three enzymes (4-coumarate CoA ligase, malonyl-CoA synthetase and engineered benzoate CoA ligase) along with synthetic chemistry was practiced to synthesize starter and extender substrates for STS. Of these, the crystal structures of benzoate CoA ligase (BadA) from Rhodopseudomonas palustris in an apo form or in complex with a 2-chloro-1,3-thiazole-5-carboxyl-AMP or 2-methylthiazole-5-carboxyl-AMP intermediate were determined at resolutions of 1.57 Å, 1.7 Å, and 2.13 Å, respectively, which reinforces its capacity in production of unusual CoA starters. STS exhibits broad substrate promiscuity effectively affording structurally diverse polyketide products. Seven novel products showed desired cytotoxicity against a panel of cancer cell lines (A549, HCT116, Cal27). With the treatment of two selected compounds, the cancer cells underwent cell apoptosis in a dose-dependent manner. The precursor-directed biosynthesis alongside structure-guided enzyme engineering greatly expands the pharmaceutical repertoire of lead compounds with promising/enhanced biological activities.

Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C–C or N–C covalent linkage. Here, we report four structurally attractive diterpene–alkaloid conjugates polyalongarins A–D (1–4), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula. In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine the chemical structures and stereo-configurations of 1. Compounds 1–4 were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC₅₀ (2.8–6.4 μM) and CC₅₀ values (50.4–200 μM). The inhibitory mechanism of 1–4 on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of 1–4 and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane–aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors.

And Aim: Coptidis Rhizoma extract (CRE) is a traditional herbal medicine commonly used to treat insomnia and cognitive deficits. However, its protective effects and underlying molecular mechanisms in conditions such as sleep deprivation (SD) are not fully understood. This study intended to elucidate these mechanisms by combining functional assessments, imaging techniques, and genomic analyses in an animal model of sleep fragmentation-induced cognitive impairment. CRE's efficacy was compared with melatonin, an established neuroprotective agent. Our results demonstrated that SD significantly impaired cognitive functions and induced oxidative stress, inflammation, and multiple forms of neuronal cell death. Additionally, SD disrupted growth hormone (Gh) and hemoglobin (Hb) synthesis, impaired glymphatic clearance, and promoted accumulation of amyloid β-peptide (Aβ_1-42), collectively contributing to neuronal inflammation and degeneration. Oral administration of CRE (0.5-1.5 g/kg/day) and intraperitoneal melatonin (10 mg/kg/day) for 15 days effectively reversed these adverse effects by restoring Gh and Hb synthesis, TH- and DCX-positive neurons, and glymphatic function, reducing inflammation and neurodegeneration, and normalizing genes and proteins involved in neurotransmission, oxygen transport, DNA repair, cellular metabolism, structural integrity, and neuronal function. However, neither treatment restored the downregulated expression of Gh-related genes, indicating limited effects on hypothalamic-pituitary regulation. In conclusion, these findings highlight the potential therapeutic role of CRE in alleviating cognitive and physiological impairments caused by sleep deprivation.