In vitro and in silico cholinesterase inhibitory potential of metabolites from Laurencia snackeyi (Weber-van Bosse) M. Masuda.

Alzheimer's disease (AD) is a neurodegenerative disease that causes deterioration in intelligence and psychological activities. Yet, till today, no cure is available for AD. The marine environment is an important sink of bioactive compounds with neuroprotective potential with reduced adverse effects. Recently, we collected the red algae Laurencia snackeyi from Terumbu Island, Malaysia which is known to be rich in halogenated metabolites making it the most sought-after red algae for pharmaceutical studies. The red alga was identified based on basic morphological characteristics, microscopic observation and chemical data from literature. The purplish-brown algae was confirmed a new record. In Malaysia, this species is poorly documented in Peninsular Malaysia as compared to its eastern continent Borneo. Thus, this study intended to investigate the diversity of secondary metabolites present in the alga and its cholinesterase inhibiting potential for AD. The extract inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of  14.45 ± 0.34 µg mL-1 and 39.59 ± 0.24 µg mL-1, respectively. Subsequently, we isolated the synderanes, palisadin A (1), aplysistatin (2) and 5-acetoxypalisadin B (3) that was not exhibit potential. Mass spectrometry analysis detected at total of 33 additional metabolites. The computational aided molecular docking using the AChE and BChE receptors on all metabolites shortlisted 5,8,11,14-eicosatetraynoic acid (31) and 15-hydroxy-1-[2-(hydroxymethyl)-1-piperidinyl]prost-13-ene-1,9-dione (42) with best inhibitory properties, respectively with the lowest optimal combination of S-score and RMSD values. This study shows the unexplored potential of marine natural resources, however, obtaining sufficient biomass for detailed investigation is an uphill task. Regardless, there is a lot of potential for future prospects with a wide range of marine natural resources to study and the incorporation of synthetic chemistry, in vivo studies in experimental design. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03725-6.

Antimicrobial Potential of Aqueous Extract of Giant Sword Fern and Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry Analysis.

Vibriosis and parasitic leech infestations cause the death of various farmed fish, such as groupers, hybrid groupers, sea bass, etc., in Malaysia and other Southeast Asian countries. In the absence of natural control agents, aquaculture operators rely on toxic chemicals to control Vibrio infections and parasitic leeches, which can have a negative impact on the environment and health. In the present study, we investigated the antivibrio and antiparasitic activities of the aqueous extract of giant sword fern (GSF) (Nephrolepis biserrata, Nephrolepidaceae, locally known as "Paku Pedang") against four Vibrio spp. and the parasitic leech Zeylanicobdella arugamensis, as well as its metabolic composition using the ultra-high-performance liquid chromatography-high-resolution mass spectrometry system (UHPLC-HRMS). The data show that the aqueous extract of GSF at a concentration of 100 mg/mL exhibits potent bactericidal activity against V. parahaemolyticus with a zone of inhibition of 19.5 mm. In addition, the extract showed dose-dependent activity against leeches, resulting in the complete killing of the parasitic leeches within a short period of 11-43 min when tested at concentrations ranging from 100 to 25 mg/mL. The UHPLC-HRMS analysis detected 118 metabolites in the aqueous extract of GSF. Flavonoids were the primary metabolites, followed by phenolic, aromatic, fatty acyl, terpenoid, vitamin and steroidal compounds. Notably, several of these metabolites possess antibacterial and antiparasitic properties, including cinnamaldehyde, cinnamic acid, apigenin, quercetin, cynaroside, luteolin, naringenin, wogonin, 6-gingerol, nicotinamide, abscisic acid, daidzein, salvianolic acid B, etc. Overall, our study shows the significant antibacterial and antiparasitic potential of the GSF aqueous extract, which demonstrates the presence of valuable secondary metabolites. Consequently, the aqueous extract is a promising natural alternative for the effective control of Vibrio infections and the treatment of parasitic leeches in aquaculture systems.

Therapeutic Potential and Nutraceutical Profiling of North Bornean Seaweeds: A Review.

Malaysia has a long coastline surrounded by various islands, including North Borneo, that provide a suitable environment for the growth of diverse species of seaweeds. Some of the important North Bornean seaweed species are Kappaphycus alvarezii, Eucheuma denticulatum, Halymenia durvillaei (Rhodophyta), Caulerpa lentillifera, Caulerpa racemosa (Chlorophyta), Dictyota dichotoma and Sargassum polycystum (Ochrophyta). This review aims to highlight the therapeutic potential of North Bornean seaweeds and their nutraceutical profiling. North Bornean seaweeds have demonstrated anti-inflammatory, antioxidant, antimicrobial, anticancer, cardiovascular protective, neuroprotective, renal protective and hepatic protective potentials. The protective roles of the seaweeds might be due to the presence of a wide variety of nutraceuticals, including phthalic anhydride, 3,4-ethylenedioxythiophene, 2-pentylthiophene, furoic acid (K. alvarezii), eicosapentaenoic acid, palmitoleic acid, fucoxanthin, ß-carotene (E. denticulatum), eucalyptol, oleic acid, dodecanal, pentadecane (H. durvillaei), canthaxanthin, oleic acid, pentadecanoic acid, eicosane (C. lentillifera), pseudoephedrine, palmitic acid, monocaprin (C. racemosa), dictyohydroperoxide, squalene, fucosterol, saringosterol (D. dichotoma), and lutein, neophytadiene, cholest-4-en-3-one and cis-vaccenic acid (S. polycystum). Extensive studies on the seaweed isolates are highly recommended to understand their bioactivity and mechanisms of action, while highlighting their commercialization potential.

Withanolides, the hidden gem in Physalis minima: A mini review on their anti-inflammatory, anti-neuroinflammatory and anti-cancer effects.

The Southeast Asian rainforests, notably in East Malaysia, are home to a diverse range of medicinal plant species with limitless therapeutic potential. Physalis minima (family Solanaceae) is a native East Malaysia plant which is closely linked to P. angulata, are recognized for their various pharmacology properties are abundance in Withanolides, a C28-steroidal lactones based on an ergostane skeleton. This review focuses on the bioactive compounds of this herb, as it is frequently used to treat inflammation, neurodegenerative disease and cancer among East Malaysian ethnic groups. In this review, a total of 103 Withanolides were reported, with 59 of them being newly characterized. Previous scientific data revealed that Withanolides were intriguing principal compounds for inflammatory, neuroinflammatory and cancer treatment due to unique steroidal structure and strong bioactivities. Despite their excellent pharmacological characteristics, only a few Withanolides have been extensively studied, and the majority of them, particularly the newly discovered Withanolides, remained unknown for their therapeutic properties. This indicates that P. minima compounds are worth to be investigate for its pharmacological effects.

Efficacy of the Aqueous Extract of Azadirachta indica Against the Marine Parasitic Leech and Its Phytochemical Profiling.

Zeylanicobdella arugamensis (Hirudinea), a marine parasitic leech, not only resulted in the mortality of the host fish (Groupers) but also caused economic losses. The current study aimed to elucidate the antiparasitic efficacy of the aqueous extract of the Azadirachta indica leaves against Z. arugamensis and to profile the composition via LC-Q Exactive HF Orbitrap mass spectrometry. Different concentrations (25, 50 and 100 mg/mL) of A. indica extract were prepared and tested on the parasitic leeches. The total mortality of leeches was noticed with an exposure to the A. indica aqueous extract. The average times required for the aqueous extract at concentrations of 25, 50 and 100 mg/mL to kill the leeches were 42.65 ± 9.20, 11.69 ± 1.11 and 6.45 ± 0.45 min, respectively, in a dose-dependent manner. The Orbitrap mass spectrometry analysis indicated the presence of five flavonoids (myricetin 3-O-galactoside, trifolin, isorhamnetin, quercetin and kaempferol), four aromatics (4-methoxy benzaldehyde, scopoletin, indole-3-acrylic acid and 2,4-quinolinediol), three phenolics (p-coumaric acid, ferulic acid and phloretin) and two terpenoids (pulegone and caryophyllene oxide). Thus, our study indicates that A. indica aqueous extract is a good source of metabolites with the potential to act as a biocontrol agent against the marine parasitic leech in aquaculture.

Antiparasitic Potential of Chromatographic Fractions of Nephrolepis biserrata and Liquid Chromatography-Quadrupole Time-of-Flight-Mass Spectrometry Analysis.

Marine aquaculture development is recently impeded by parasitic leech Zeylanicobdella arugamensis (Hirudinea, Piscicolidae) in Sabah, Malaysia. The parasitic leech infests a variety of cultured fishes in aquaculture facilities. In this study, we evaluated the antiparasitic activity of the chromatographic fractions of the medicinal plant Nephrolepis biserrata methanol extract against Z. arugamensis and highlighted the potential metabolites responsible for the antiparasitic properties through liquid chromatography (LC)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS) analysis. Out of seven fractions obtained through flash column chromatography techniques, three fractions demonstrated antiparasitic properties. Significant parasitic mortality was indicated by fraction 3 at a concentration of 2.50 mg/mL, all the leeches were killed in a time limit of 1.92 ± 0.59 min. followed by fraction 4 (14 mg/mL) in 34.57 ± 3.39 and fraction 5 (15.3 mg/mL) in 36.82 ± 4.53 min. LC-QTOF-MS analysis indicated the presence of secondary metabolites including phytosphingosine (6), pyrethrosin (1), haplophytine (9), ivalin (2), warburganal (3), isodomedin (4) and pheophorbide a (16), representing sphingoid, alkaloid, terpenoid, phenolic and flavonoid groups. Thus, our study indicated that the chromatographic fractions of N. biserrata demonstrated significant antiparasitic activity against the marine parasitic leeches due to the presence of potent antiparasitic bioactive compounds.

Antiparasitic potential of Nephrolepis biserrata methanol extract against the parasitic leech Zeylanicobdella arugamensis (Hirudinea) and LC-QTOF analysis.

Marine leech Zeylanicobdella arugamensis (Piscicolidae), an economically important parasite is infesting predominantly cultured groupers, hybrid groupers and other fish in Southeast Asian countries. In this study, we tested the anti-parasitic potential of a medicinal plant Nephrolepis biserrata found in Sabah, East Malaysia against Z. arugamensis. Various concentrations of methanol extracts of the plant were tested experimentally against Z. arugamensis and disinfestation of the leech from its primary host hybrid groupers. The composition of methanol extract of N. biserrata was determined through LC-QTOF analysis. The significant anti-parasitic activity of 100% mortality of leeches was observed with the exposure of N. biserrata extracts. The average time to kill the leeches at concentrations of 25, 50 and 100 mg/ml was 25.11 ± 3.26, 11.91 ± 0.99, and 4.88 ± 0.50 min., respectively. Further, at various low concentrations of N. biserrata 2.5, 5 and 10 mg/ml, hybrid groupers were disinfested in an average time of 108.33 ± 12.65, 65.83 ± 9.70 and 29.16 ± 5.85 min., respectively. The tandem mass spectrometry data from LC-QTOF indicated some hits on useful bioactive compounds such as terpenoids (ivalin, isovelleral, brassinolide, and eschscholtzxanthin), flavonoids (alnustin, kaempferol 7,4'-dimethyl ether, and pachypodol), phenolics (piscidic acid, chlorogenic acid, and ankorine), and aromatic (3-hydroxycoumarin). Thus N. biserrata can act as a potential biocontrol agent.

MS-based metabolomics revealing Bornean Sinularia sp. extract dysregulated lipids triggering programmed cell death in Hepatocellular carcinoma.

Soft coral, Sinularia sp. had been proven to inherit promising anti-cancer properties against variety of cancer. Current study, Sinularia sp. extract was introduced to Hepatocellular carcinoma (Hep 3B). Cell viability assay indicated the extract exhibit a dose and time dependent cytotoxicity. LC50 exhibited the lowest at 72 h post treatment estimated as 45.3 µg/mL. Morphological alterations including nuclear condensation, cytoplasm shrinkage and deformed cellular shape in treated Hep 3B were observable. Chemometric analysis revealed hydrophobic metabolites were significantly altered. Elevated vitamin D and derivatives tend to up-regulation Ca2+ and ROS subsequently triggering apoptosis. Dysregulated glycerolipids may suggest that they were biotransformed to compensate the needs of phospholipids during cell damage. Perturbation of sphingolipids, ceramide and carbohydrate-conjugated ceramides species increased the release of pro-apoptotic components reside within mitochondria and promote programmed cell death in treated Hep 3B. To conclude, MS-based metabolomics enabled the characterization of Sinularia sp. extract-induced cell death.