Over the years, the biological activities of seaweeds could have piqued research interest due to their specific functional phytochemistry, which may not be available in terrestrial plants. Seaweeds produce these compounds to overcome and control stressful biotic and abiotic conditions. Additionally, they are potentially excellent sources of highly useful leads in the development of new drugs. Our study aims to unveil, for the first time, an overview of Halopteris scoparia, a species belonging to the Phaeophyceae class and the Stypocaulacea family, by summarizing all available literature data. In this work, we attempt to shed light on its phytochemistry, nutritional values, pharmacological activities, and industrial uses and applications. To gather information related to H. scoparia, relevant keywords were used to search internet databases including Google Scholar, PubMed, ResearchGate, Web of Science, Algae Database, WoRMS database, and DORIS database. The chemical structures were drawn using Chemdraw and verified using the PubChem database. Chemically, this species contains a wide variety of secondary metabolites, such as terpenoids and phenolic compounds. Additionally, other chemical components with nutraceutical value have been identified, such as carbohydrates, proteins, lipids, pigments, minerals and mycosporine like amino acids. Then, holding several reported pharmacological properties, including antioxidant, anti-inflammatory, cytotoxic, dermoprotective, antidepressive, antibacterial, antibiofilm, antifungal, anti-parasitic activities and acute toxicity. In addition to other their applications such as bioconversion and antifouling activities. To confirm the previous pharmacological properties, more comprehensive and systematic in vivo, preclinical, and clinical studies are needed. Furthermore, research is required to uncover the mechanisms of its active compounds and their potential therapeutic effects in treating other diseases such as atherosclerosis, neurodegenerative diseases, and viral infections.
The in vivo and in vitro mechanistic anti-inflammatory actions of cucurbitacin E (CE) (Citrullus lanatus var. citroides) were examined. The results showed that LPS/INF-γ increased NO production in RAW264.7 macrophages, whereas L-NAME and CE curtailed it. CE did not reveal any cytotoxicity on RAW264.7 and WRL-68 cells. CE inhibited both COX enzymes with more selectivity toward COX-2. Intraperitoneal injection of CE significantly suppressed carrageenan-induced rat's paw edema. ORAC and FRAP assays showed that CE is not a potent ROS scavenger. It could be concluded that CE is potentially useful in treating inflammation through the inhibition of COX and RNS but not ROS.
Goniothalamus macrophyllus (Blume) Hook. f. & Thoms. is a plant widely distributed in Malaysia. The aim of this study is to identify compounds from the roots of G. macrophyllus. The ground roots were extracted with aqueous methanol and partitioned sequentially with n-hexane, chloroform and butanol. Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene-A (1), -B (2). The absolute configuration of goniolandrene B (2) was established by circular dichrosim. The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0.42 to 160 μM. Goniothalamin (3) exhibited the highest inhibition of 0.42 μM.
In our quest to discover advanced glycation end products (AGEs) inhibitors from Clinacanthus nutans (Burm.f.) Lindau leaves, we conducted a bioactivity-based molecular networking. This approach integrates LC-MS2 profiling and in vitro antiglycation data to predict bioactive compounds. We began by screening three extracts: 100% ethanol, 70% ethanol and 100% water alongside the in vitro antioxidant activity, total phenolics content (TPC) and schaftoside content. Among these extracts, 100% ethanol extract exhibited the highest total AGEs inhibition effects (IC50 = 80.18 ± 11.6 μg/mL), DPPH scavenging activity (IC50 = 747.40 ± 10.30 μg/mL) and TPC (26.54 ± 2.09 μg GAE /mg extract). Intriguingly, 100% ethanol extract contained the lowest amount of schaftoside, suggesting the involvement of other phytochemicals in the antiglycation effects. The molecular networking and in silico structural annotations of 401 LC-MS features detected in the fractions from 100% ethanol extract predicted 21 bioactive compounds (p 0.90), including several C40 carotenoids, alkaloids containing tetrapyrrole structures and fatty acids. On the contrary, all phenolics showed weak correlations with antiglycation effects. These predictions were further validated in vitro, where carotenoid lutein showed half maximal inhibitory concentration, IC50 = 96 ± 8 μM and selected flavonoid-C-glycosides exhibited weaker inhibitions (IC50 between 568 and 1922 μM). Notably, lutein content was higher in freeze-dried leaves (12.42 ± 0.82 mg/100 g) than oven-dried, although the former was associated with elevated mercury levels. In summary, C. nutans exhibited potential antiglycation and antioxidant activity, and lutein was identified as the main bioactive principle.
3,4',5-Trihydroxy-3',7-dimethoxyflavanone was isolated from the ligroin extract of the leaves of Blumea balsamifera, while the acetone extract yielded 3',4',5-trihydroxy-7-methoxyflavanone and a new biflavonoid identifed as 3-O-7''-biluteolin (1). The isolation of 1 is significant since a biflavonoid with a C-O-C linkage of the type [I-3-O-II-7] has not been previously reported from a plant.
Ficus deltoidea was known for its potent antioxidant, anti-melanogenic and photoprotective skin barrier activities. These properties are contributed by its biomarkers which are vitexin and isovitexin. This study aims to optimize the yield of methanolic extraction of Ficus deltoidea leaves (EFD) and evaluate their effects on skin barrier function and hydration. For optimization, Box-Behnken design was utilized to investigate the effects of methanol concentration, sonication time, and solvent-to-sample ratio on the yields of vitexin and isovitexin in EFD. The optimal yields obtained were 32.29 mg/g for vitexin and 35.87 mg/g for isovitexin. The optimum extraction conditions were 77.66% methanol concentration, 20.03 min sonication time, and 19.88 mL/g solvent-to-sample ratio. The quantitative real-time polymerase chain reaction was utilized to measure variant marker genes of transglutaminase-1, caspase 14, ceramide synthase 3, involucrin, and filaggrin of EFD-induced keratinocyte differentiation by in vitro study. Exposure to EFD has elevated the mRNA levels of all tested marker genes by 0.7-9.2 folds. Then, in vivo efficacy study was conducted on 20 female subjects for 14 days to evaluate skin biophysical assessment of hydration. EFD topical formulation treatment successfully increased skin hydration on day 7 (43.74%) and day 14 (47.23%). In silico study by molecular docking was performed to identify intermolecular binding interactions of vitexin and isovitexin with the interested proteins of tested marker genes. The result of molecular docking to the interested proteins revealed a similar trend with real-time PCR data. In conclusion, EFD potentially enhanced the skin barrier function and hydration of human skin cells.
Plumbagin, isoshinanolone, epishinanolone, shinanolone, quercetin and kaempferol were isolated from the leaves of Nepenthes gracilis. Spectral data of shinanolone are presented.
A study on the leaves of Aglaia exima led to the isolation of one new and seven known compounds: six triterpenoids and two steroids. Their structures were elucidated and analyzed mainly by using spectroscopic methods; 1D and 2D NMR, mass spectrometry, UV spectrometry and X-ray. All the triterpenoids and steroids were measured in vitro for their cytotoxic activities against eight cancer cell lines; lung (A549), prostate (DU-145), skin (SK-MEL-5), pancreatic (BxPC-3), liver (Hep G2), colon (HT-29), breast (MCF-7) and (MDA-MB-231). The new cycloartane triterpenoid, 24(E)-cycloart-24-ene-26-ol-3-one 1, showed potent cytotoxic activity against colon (HT-29) cancer cell line (IC(50) 11.5μM).
The bark of Cryptocarya crassinervia provided two new phenantrene alkaloids, 2-hydroxyatherosperminine (1) and N-demethyl-2-methoxyatherosperminine (2).
Type 2 diabetes (T2D) remains a major chronic metabolic disorder affecting hundreds of millions of the global population, mostly among adults, engendering high rates of morbidity and mortality. It is characterized by complex aetiologies including insulin deficiency and resistance, and hyperglycemia, and these significantly constitute therapeutic challenges. Several pathways have been implicated in its pathophysiology and treatment including the epigenetic regulatory mechanism, notably, deoxyribonucleic acid (DNA) methylation/demethylation, histone modification, non-coding ribonucleic acid (ncRNA) modulation and other relevant pathways. Many studies have recently documented the implications of phytochemicals on the aforementioned biomarkers in the pathogenesis and treatment of T2D. In this review, the cellular and molecular mechanisms of the epigenetic effects of some bioactive alkaloidal and phenolic phytochemicals as potential therapeutic alternatives for T2D have been overviewed from the recent literature (2019-2024). From the survey, the natural product-based compounds, C1-C32 were curated as potent epigenetic modulators for T2D. Their cellular and molecular mechanisms of anti-T2D activities with relevant epigenetic biomarkers were revealed. Although, more comprehensive experimental analyses are observably required for validating their activity and toxicological indices. Thus, perspectives and challenges were enumerated for such demanding future translational studies. The review reveals advances in scientific efforts towards reversing the global trend of T2D through epigenetic phytotherapeutics.
A phytochemical study of the EtOAc-soluble part of the methanolic extract of the bark of Endiandra kingiana led to the isolation of three new pentacyclic kingianins as racemic mixtures, kingianins O-Q (1-3), together with the known kingianins A, F, K, L, M and N (4-9), respectively. The structures of the new kingianins 1-3 were determined by 1D and 2D NMR analysis in combination with HRESIMS experiments. Kingianins A-Q were assayed for Mcl-1 binding affinity. Kingianins G and H were found to be potent inhibitors of Mcl-1/Bid interaction. A structure-activity relationship study showed that potency is very sensitive to the substitution pattern on the pentacyclic core. In addition, in contrast with the binding affinity for Bcl-xL, the levorotatory enantiomers of kingianins G, H and J exhibited similar binding affinities for Mcl-1 than their dextrorotatory counterparts, indicating that the two anti-apoptotic proteins have slightly different binding profiles.
Today, pharmaceutical drugs have been shown to have serious side effects, while the bioactive components of botanical plants are proven to be effective in the treatment of several diseases marked by enhanced oxidative stress and mild inflammation, often associated with minimal adverse events. Coumaroyltyramine, designated by various nomenclatures such as paprazine, N-p-trans-coumaroyltyramine, p-coumaroyltyramine and N-p-coumaroyltyramine, could be a promising bioactive ingredient to address health issues thanks to its powerful anti-inflammatory and antioxidant effects. This review represents the first in-depth analysis of coumaroyltyramine, an intriguing phenylpropanoid substance found in many species of plants. In fact, an in-depth examination of coumaroyltyramine's biological characteristics, chemical attributes, and synthesis process has been undertaken. All previous research relating to the discovery, extraction, biosynthesis, and characterization of the biologically and pharmacologically active properties of coumaroyltyramine has been reviewed and taken into consideration in this analysis. All articles published in a peer-reviewed English-language journal were examined between the initial compilations of the appropriate database until February 12, 2024. A variety of phytochemicals revealed that coumaroyltyramine is a neutral amide of hydroxycinnamic acid that tends to concentrate in plants as a reaction against infection caused by pathogens and is extracted from several medicinal herbs such as Cannabis sativa, Solanum melongena, Allium bakeri, Annona cherimola, Polygonatum zanlanscianense, and Lycopersicon esculentum. Thanks to its effectiveness in suppressing the effect of the enzyme α-glucosidase, coumaroltyramine has demonstrated antihyperglycemic activity and could have an impact on diabetes and metabolic disorders. It has considerable anti-inflammatory and antioxidant effects. These results were obtained through biological and pharmacological studies in silico, in vivo, and in vitro. In addition, coumaroyltyramine has demonstrated hypocholesterolemic and neuroprotective benefits, thereby diminishing heart and vascular disease incidence and helping to prevent neurological disorders. Other interesting properties of coumaroltyramine include anticancer, antibacterial, anti-urease, antifungal, antiviral, and antidysmenorrheal activities. Targeted pathways encompass activity at different molecular levels, notably through induction of endoplasmic reticulum stress-dependent apoptosis, arrest of the cell cycle, and inhibition of the growth of cancer cells, survival, and proliferation. Although the findings from in silico, in vivo, and in vitro experiments illustrate coumaroyltyramine's properties and modes of action, further research is needed to fully exploit its therapeutic potential. To improve our understanding of the compound's pharmacodynamic effects and pharmacokinetic routes, large-scale research should first be undertaken. To determine whether coumaroyltyramine is clinically safe and effective, further studies are required in the clinical and toxicological fields. This upcoming research will be crucial to achieving the overall potency of this substance as a natural drug and in terms of its potential synergies with other drugs.
Eurycoma longifolia Jack is an herbal medicinal plant of South-East Asian origin, popularly recognized as 'Tongkat Ali.' The plant parts have been traditionally used for its antimalarial, aphrodisiac, anti-diabetic, antimicrobial and anti-pyretic activities, which have also been proved scientifically. The plant parts are rich in various bioactive compounds (like eurycomaoside, eurycolactone, eurycomalactone, eurycomanone, and pasakbumin-B) among which the alkaloids and quassinoids form a major portion. Even though toxicity and safety evaluation studies have been pursued, still a major gap exists in providing scientific base for commercial utilization and clearance of the Tongkat Ali products with regard to consumer's safety. The present review aims at reviewing the research works undertaken till date, on this plant in order to provide sufficient baseline information for future works and for commercial exploitation.
Cardamonin is a natural chalcone that has been shown to exhibit high anticancer activity. In an attempt to discover analogues of cardamonin with enhanced anticancer activity, 19 analogues were synthesized and tested against A549 and HK1 cell lines. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin's phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active analogue possessing IC50 values of 13.2μM and 0.7μM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. It was also able to significantly inhibit the migration of A549 and HK1 cells. Further mode of action studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These events further led to the induction of apoptosis by the compound via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which indicated that it exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway.
Usually isolated from Garcinia (Clusiaceae) or Hypericum (Hypericaceae) species, some Polycyclic Polyprenylated AcylPhloroglucinols (PPAPs) have been recently reported as potential research tools for immunotherapy. Aiming at exploring the chemodiversity of PPAPs amongst Garcinia genus, a dereplication process suitable for such natural compounds has been developed. Although less sensitive than mass spectrometry, NMR spectroscopy is perfectly reproducible and allows stereoisomers distinction, justifying the development of 13C-NMR strategies. Dereplication requires the use of databases (DBs). To define if predicted DBs were accurate enough as dereplication tools, experimental and predicted δC of natural products usually isolated from Clusiaceae were compared. The ACD/Labs commercial software allowed to predict 73% of δC in a 1.25 ppm range around the experimental values. Consequently, with these parameters, the major PPAPs from a Garcinia bancana extract were successfully identified using a predicted DB.
Lipoxygenase (LOX)-inhibiting compounds from the leaves of Chisocheton polyandrus Merr. were isolated in this study using a bioactivity-guided fractionation technique. Two dammarane triterpenoids, dammara-20,24-dien-3-one (1) (IC(50)=0.69±0.07 μM) and 24-hydroxydammara-20,25-dien-3-one (2) (IC(50)=1.11±0.38 μM), were isolated and identified based on the soybean LOX assay. Dammara-20,24-dien-3-one (1) exhibited dual inhibition of both human 5-LOX (IC(50)=24.27±2.92 μM) and cyclooxygenase-2 (COX-2) (IC(50)=3.17±0.90 μM), whereas 24-hydroxydammara-20,25-dien-3-one (2) did not exhibit any significant inhibitory effects. This report is the first to detail the inhibition of LOX and COX by both C. polyandrus and its isolated compounds.
Labisia pumila is a traditional herb widely used as post-partum medication for centuries. Recently, extensive researches have been carried out on the phytochemical identification, biological and toxicological studies for the herb. Phytochemicals found in the herbal extract showed high antioxidant properties, which were essential for various pharmacological activities. The significant findings are anti-estrogenic deficiency and -immunodeficiency diseases. Another finding that has considerable impact on natural product research is the contribution of L. pumila in promoting skin collagen synthesis. The performance of the herb as anti-aging agent due to natural aging process and accelerated by UV radiation was reviewed critically.
The evolution of antibiotic resistance in Staphylococcus aureus showed that there is no long-lasting remedy against this pathogen. The limited number of antibacterial classes and the common occurrence of cross-resistance within and between classes reinforce the urgent need to discover new compounds targeting novel cellular functions not yet targeted by currently used drugs. One of the experimental approaches used to discover novel antibacterials and their in vitro targets is natural product screening. Three known pentacyclic triterpenoids were isolated for the first time from the bark of Callicarpa farinosa Roxb. (Verbenaceae) and identified as α-amyrin [3β-hydroxy-urs-12-en-3-ol], betulinic acid [3β-hydroxy-20(29)-lupaene-28-oic acid], and betulinaldehyde [3β-hydroxy-20(29)-lupen-28-al]. These compounds exhibited antimicrobial activities against reference and clinical strains of methicillin-resistant (MRSA) and methicillin-sensitive S. aureus (MSSA), with minimum inhibitory concentration (MIC) ranging from 2 to 512 μg/mL. From the genome-wide transcriptomic analysis to elucidate the antimicrobial effects of these compounds, multiple novel cellular targets in cell division, two-component system, ABC transporters, fatty acid biosynthesis, peptidoglycan biosynthesis, aminoacyl-tRNA synthetases, ribosomes and β-lactam resistance pathways are affected, resulting in destabilization of the bacterial cell membrane, halt in protein synthesis, and inhibition of cell growth that eventually lead to cell death. The novel targets in these essential pathways could be further explored in the development of therapeutic compounds for the treatment of S. aureus infections and help mitigate resistance development due to target alterations.
Benign prostate hyperplasia (BPH) is an enlargement of the prostate gland, because of hormonal changes in aging males which contribute significantly to excessive proliferation over apoptosis of prostatic cells. The anti-proliferative and induced apoptotic activities of Eurycoma longifolia quassinoids on cancer cell lines could be promising therapeutic targets on BPH. Hitherto, no report of the quassinoids against BPH problem was available. In this study, a systematic phytochemical fractionation of the root extract, TAF2 was performed, which led to the discovery of nine previously described C20 quassinoids (1-9). Two undescribed C20 (10 and 12) and one undescribed (11) C19 quassinoids were identified by detailed NMR and HR-ESI-MS data analysis. Their absolute configurations were assigned by ECD spectral analysis. The quassinoids (1-12) were tested for inhibitory activity against the proliferation of human BPH-1 and human skin Hs27 fibroblast cells cultured in vitro. 1, 2 and 3 at 10 μM significantly reduced BPH-1 cell viability and were cytotoxic to Hs27 fibroblast cells. 2 was selected for further study of anti-BPH activity against testosterone induced BPH rats. At 5 mg/kg, 2 reduced the rat prostatic weight and prostatic index, consistent with the decrease in papillary acini number and epithelial thickness of the prostate tissues. These quassinoids may be potential anti-BPH compounds that require further studies.
Malaysian Gelam honey has anti-inflammatory and antibacterial properties, a high antioxidant capacity, and free radical-scavenging activity. Lipopolysaccharide (LPS) stimulates immune cells to sequentially release early pro- and anti-inflammatory cytokines and induces the synthesis of several related enzymes. The aim of this study was to investigate the effect of the intravenous injection of honey in rats with LPS-induced endotoxemia. The results showed that after 4h of treatment, honey reduced cytokine (tumor necrosis factor-α, interleukins 1β, and 10) and NO levels and increased heme oxygenase-1 levels. After 24h, a decrease in cytokines and NO and an increase in HO-1 were seen in all groups, whereas a reduction in HMGB1 occurred only in the honey-treated groups. These results support the further examination of honey as a natural compound for the treatment of a wide range of inflammatory diseases.