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"Kijjoa, Anake"
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Integration of Network Pharmacology, Molecular Docking, and In Vitro Nitric Oxide Inhibition Assay to Explore the Mechanism of Action of Thai Traditional Polyherbal Remedy, Mo-Ha-Rak, in the Treatment of Prolonged Fever
by
Rattarom, Ruchilak
,
Chaloemram, Chinnaphat
,
Nualkaew, Somsak
in
anti-inflammatory
,
Care and treatment
,
Chemical properties
2025
Background: Prolonged fever (PF) is one of the most challenging clinical conditions due to its complex molecular mechanisms and limited effective treatments. Objective: The current study aimed to explore the mechanism of action of Mo-Ha-Rak (MHR), a Thai traditional polyherbal remedy, in PF treatment. Methods: Integration of network pharmacology, molecular docking, and inhibition of nitric oxide (NO) production in LPS-induced RAW264.7 macrophages approaches were used. Results: The study identified 86 potential active compounds, 131 potential therapeutic targets, and 9 hub genes for MHR. Key targets with the highest degree of connectivity in PF, including TNF, IL6, IL1B, PTGS2, STAT3, and NFKB1, are closely associated with arachidonic acid metabolism pathways, which play critical roles in infections, inflammation, cell proliferation, and apoptosis in the PF microenvironment. Molecular docking analysis suggested that core compounds exhibited strong binding affinities for four key targets, viz. TNF, IL6, IL1B, and PTGS2, with binding energies ranging from −4.1 to −9.8 kJ/mol. MHR exhibited dose-dependent reduction of NO production at concentrations of 10–100 µg/mL. Among the biomarkers of MHR tested, ellagic acid, loureirin A, resveratrol, and rhein showed potential to inhibit NO production. Conclusions: This study demonstrates that MHR exerts its therapeutic effects on PF through a complex network of multiple compounds, targets, and pathways. These findings highlight the mechanisms of PF and the role of MHR in modulating the arachidonic acid metabolism pathway, which underlies the development of fever.
Journal Article
In Vitro and In Vivo Anti-Phytopathogenic Fungal Activity of a Culture Extract of the Marine-Derived Fungus, Aspergillus unguis KUFA 0098, and Its Major Depsidone Constituents
2025
The crude ethyl acetate extract of the culture of a marine sponge-associated fungus,
KUFA 0098, was tested for its capacity to inhibit the growth of ten phytopathogenic fungi,
.
,
,
,
,
,
,
,
,
, and
At a concentration of 1 g/L, the crude extract was most active against
, causing the highest growth inhibition (55.32%) of this fungus but inactive against
and
. At a concentration of 10 g/L, the crude extract completely inhibited the growth of most of the fungi, except for
,
, and
, with 94.50%, 74.12%, and 67.80% of inhibition, respectively. The crude extract of
KUFA 0098 exhibited growth-inhibitory effects against
and
, causative agents of brown leaf spot disease and leaf blast disease, respectively, on rice plant var. KDML105, under greenhouse conditions. Chromatographic fractionation and purification of the extract led to the isolation of four previously described depsidones,
unguinol (
), 2-chlorounguinol (
), 2,4-dichlorounguinol (
), and folipastatin (
), as well as one polyphenol, aspergillusphenol A (
). The major compounds, i.e.,
,
, and
, were tested against the ten phytopathogenic fungi. Compounds
and
were able to inhibit growth of most of the fungi, except
, and
. Compound
showed the same minimum inhibitory concentration (MIC) values as that of carbendazim against
,
,
, and
, while compound
showed the same MIC values as that of carbendazim against only
and
. Compound
was not active against all of the ten phytopathogenic fungi tested.
Journal Article
New Bicyclic Sesquiterpene and Labdane Diterpenes from the Culture Extract of the Sea Grass-Derived Fungus Penicillium verruculosum KUFA1509
2026
An unreported bicyclic sesquiterpene acid, verruculosic acid (
), was isolated together with the previously reported labdane diterpenes, (+)-agathic acid (
) and hypoxyterpenoid A (
), one 3-
-2,3-seco-labdane, penioxalicin (
), and 5-carboxyphthalide (
), from a sea grass-associated fungus,
KUFA1509. The structures of the isolated compounds were elucidated by detailed analyses of 1D and 2D NMR and HRMS data. The absolute configurations of the stereogenic carbons in
and
were established by X-ray crystallography. The crystal structure of
, which was obtained for the first time, was used to prove its structure and confirm its stereochemistry. The crystal structure of
was also obtained; however, the value of its flack parameter does not allow us to determine the absolute configuration. Compound
exhibited stronger inhibitory activity than the positive control, diclofenac sodium, against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, while
and
were slightly less active than the positive control. In contrast,
exhibited much weaker activity than
. Compounds
-
were also assayed for antibacterial activity against reference and multidrug-resistant strains, but none exhibited antibacterial activity against the tested strains. Thus, the labdane skeleton could be considered as a potential scaffold for the development of anti-inflammatory agents through NO inhibition.
Journal Article
Marine-Derived Compounds with Potential Use as Cosmeceuticals and Nutricosmetics
2020
The cosmetic industry is among the fastest growing industries in the last decade. As the beauty concepts have been revolutionized, many terms have been coined to accompany the innovation of this industry, since the beauty products are not just confined to those that are applied to protect and enhance the appearance of the human body. Consequently, the terms such as cosmeceuticals and nutricosmetics have emerged to give a notion of the health benefits of the products that create the beauty from inside to outside. In the past years, natural products-based cosmeceuticals have gained a huge amount of attention not only from researchers but also from the public due to the general belief that they are harmless. Notably, in recent years, the demand for cosmeceuticals from the marine resources has been exponentially on the rise due to their unique chemical and biological properties that are not found in terrestrial resources. Therefore, the present review addresses the importance of marine-derived compounds, stressing new chemical entities with cosmeceutical potential from the marine natural resources and their mechanisms of action by which these compounds exert on the body functions as well as their related health benefits. Marine environments are the most important reservoir of biodiversity that provide biologically active substances whose potential is still to be discovered for application as pharmaceuticals, nutraceuticals, and cosmeceuticals. Marine organisms are not only an important renewable source of valuable bulk compounds used in cosmetic industry such as agar and carrageenan, which are used as gelling and thickening agents to increase the viscosity of cosmetic formulations, but also of small molecules such as ectoine (to promote skin hydration), trichodin A (to prevent product alteration caused by microbial contamination), and mytiloxanthin (as a coloring agent). Marine-derived molecules can also function as active ingredients, being the main compounds that determine the function of cosmeceuticals such as anti-tyrosinase (kojic acid), antiacne (sargafuran), whitening (chrysophanol), UV protection (scytonemin, mycosporine-like amino acids (MAAs)), antioxidants, and anti-wrinkle (astaxanthin and PUFAs).
Journal Article
Anthraquinones and Their Analogues from Marine-Derived Fungi: Chemistry and Biological Activities
by
Taktaz, Fatemeh
,
Hafez Ghoran, Salar
,
Ayatollahi, Seyed Abdulmajid
in
Acremonium
,
Algae
,
Anthraquinone
2022
Anthraquinones are an interesting chemical class of polyketides since they not only exhibit a myriad of biological activities but also contribute to managing ecological roles. In this review article, we provide a current knowledge on the anthraquinoids reported from marine-derived fungi, isolated from various resources in both shallow waters such as mangrove plants and sediments of the mangrove habitat, coral reef, algae, sponges, and deep sea. This review also tentatively categorizes anthraquinone metabolites from the simplest to the most complicated scaffolds such as conjugated xanthone–anthraquinone derivatives and bianthraquinones, which have been isolated from marine-derived fungi, especially from the genera Apergillus, Penicillium, Eurotium, Altenaria, Fusarium, Stemphylium, Trichoderma, Acremonium, and other fungal strains. The present review, covering a range from 2000 to 2021, was elaborated through a comprehensive literature search using the following databases: ACS publications, Elsevier, Taylor and Francis, Wiley Online Library, MDPI, Springer, and Thieme. Thereupon, we have summarized and categorized 296 anthraquinones and their derivatives, some of which showed a variety of biological properties such as enzyme inhibition, antibacterial, antifungal, antiviral, antitubercular (against Mycobacterium tuberculosis), cytotoxic, anti-inflammatory, antifouling, and antioxidant activities. In addition, proposed biogenetic pathways of some anthraquinone derivatives are also discussed.
Journal Article
Marine-Derived Compounds with Anti-Alzheimer’s Disease Activities
by
Hafez Ghoran, Salar
,
Kijjoa, Anake
in
Acetylcholinesterase
,
acetylcholinesterase inhibitor
,
Actinobacteria
2021
Alzheimer’s disease (AD) is an irreversible and progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to perform simple tasks. As the aging population continues to increase exponentially, AD has become a big concern for society. Therefore, neuroprotective compounds are in the spotlight, as a means to tackle this problem. On the other hand, since it is believed—in many cultures—that marine organisms in an individual diet cannot only improve brain functioning, but also slow down its dysfunction, many researchers have focused on identifying neuroprotective compounds from marine resources. The fact that the marine environment is a rich source of structurally unique and biologically and pharmacologically active compounds, with unprecedented mechanisms of action, marine macroorganisms, such as tunicates, corals, sponges, algae, as well as microorganisms, such as marine-derived bacteria, actinomycetes, and fungi, have been the target sources of these compounds. Therefore, this literature review summarizes and categorizes various classes of marine-derived compounds that are able to inhibit key enzymes involved in AD, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase (BACE-1), and different kinases, together with the related pathways involved in the pathogenesis of AD. The compounds discussed herein are emerging as promising anti-AD activities for further in-depth in vitro and in vivo investigations, to gain more insight of their mechanisms of action and for the development of potential anti-AD drug leads.
Journal Article
Antidepressant-like Effects of Garcinia nigrolineata Resin Extract in a Chronic Mild Stress Mouse Model: Modulation of Monoaminergic and HPA-Axis Pathways
by
Maneenet, Juthamart
,
Daodee, Supawadee
,
Chotritthirong, Yutthana
in
Amine oxidase (flavin-containing)
,
Analysis
,
Antidepressants
2025
The resin extract of
(GNR-E), a tropical plant used in Southeast Asian traditional medicine, was evaluated for its antidepressant-like effects in a chronic mild stress (CMS) mouse model, with imipramine as a reference drug. GNR-E dose-dependently alleviated CMS-induced anhedonia (sucrose preference test) and behavioral despair (forced swimming and tail suspension tests). Neurochemical analyses revealed that GNR-E increased serotonin (5-HT) and norepinephrine (NE) levels, reduced expression of their transporters (
,
) and receptors (
,
,
,
,
;
, 2C) in the frontal cortex and hippocampus, and normalized HPA-axis hyperactivity by lowering serum corticosterone and modulating glucocorticoid receptor (
) and
mRNA expression. In vitro, GNR-E inhibited monoamine oxidase (MAO)-A and -B (
= 2.33 and 1.55 µg/mL, respectively). Phytochemical analysis identified xanthones, particularly cowanin, as key constituents. These findings highlight GNR-E's potential as a novel plant-based antidepressant, warranting further investigation into its active compounds and clinical applications.
Journal Article
Integration of Network Pharmacology and Molecular Docking Together with an In Vitro Nitric Oxide Inhibition for the Insight for Antipyretic Effects of Benjalokawichian, the Thai Traditional Polyherbal Remedy
by
Rattarom, Ruchilak
,
Chaloemram, Chinnaphat
,
Nualkaew, Somsak
in
Amino acids
,
Animals
,
Antipyretics - chemistry
2026
Benjalokawichian (BLW) is a classic antipyretic polyherbal remedy used in Thai traditional medicine (TTM) to reduce toxic fever (TF). This study aimed to shed light on the mechanisms of action and identify bioactive components of BLW responsible for TF treatment. The methods that combine network pharmacology, molecular docking, and the inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 were employed for these objectives. Network pharmacology served as a means to identify 15 potential bioactive compounds, 88 possible therapeutic targets, and 4 hub genes related to BLW. Among the significant targets, TNF, PTGS2, STAT3, and NFKB1 were closely linked to the metabolic pathways of phenylalanine, arachidonic acid, and tyrosine, which are vital in managing infections, inflammation, proliferation, and apoptosis in the TF microenvironment. Additionally, molecular docking analysis indicated that core compounds displayed strong binding affinities for the key targets, with binding energies ranging between −4.5 and −11.1 kcal/mol. The in vitro assay demonstrated that BLW extract significantly inhibited NO production in LPS-activated RAW 264.7 macrophages, presenting an IC50 value of 69.10 μg/mL, and no cytotoxic effects on RAW 264.7 macrophages. Furthermore, the biomarker compounds of BLW extract, viz., perforatic acid and peucenin-7-methyl ether were found to decrease NO production in a dose-dependent manner. In summary, this research indicates that BLW provides therapeutic benefits for TF via a complex interplay of different compounds, targets, and pathways. These findings serve as a foundation for further research into the mechanisms of action of a polyherbal remedy toward TF to provide scientific evidences for its clinical use.
Journal Article
Chemical Diversity and Biological Activities of Meroterpenoids from Marine Derived-Fungi: A Comprehensive Update
by
Kumla, Decha
,
El-Demerdash, Amr
,
Kijjoa, Anake
in
anti-inflammatory
,
antibacterial
,
Aquatic Organisms - chemistry
2020
Meroterpenoids are a class of hybrid natural products, partially derived from a mixed terpenoid pathway. They possess remarkable structural features and relevant biological and pharmacological activities. Marine-derived fungi are a rich source of meroterpenoids featuring structural diversity varying from simple to complex molecular architectures. A combination of a structural variability and their myriad of bioactivities makes meroterpenoids an interesting class of naturally occurring compounds for chemical and pharmacological investigation. In this review, a comprehensive literature survey covering the period of 2009–2019, with 86 references, is presented focusing on chemistry and biological activities of various classes of meroterpenoids isolated from fungi obtained from different marine hosts and environments.
Journal Article
Purgative Effect, Acute Toxicity, and Quantification of Phorbol-12-Myristate-13-Acetate and Crotonic Acid in Croton tiglium L. Seeds Before and After Treatment by Thai Traditional Detoxification Process
2025
Croton tiglium L. seeds, a component of many recipes of Thai traditional medicine (TTM), had to undergo the Thai traditional detoxification process (TDP) before being used. However, this detoxification process has never been scientifically proven for its effectiveness. Thus, this research aimed to investigate the effects of TDP on purgative effect and acute toxicity, as well as the identification of some chemical constituents in C. tiglium seeds before (CB) and after (CA) treatment. The purgative effect and acute toxicity of CB and CA powders were evaluated using Wistar rats. The amounts of phorbol-12-myristate-13-acetate (PMA) and crotonic acid in the CB and CA powders were determined using HPLC. The results showed no acute toxicity in the rats administered CB and CA powders at doses of 300–2000 mg/kg of body weight (BW). However, CB and CA caused a dose-dependent increase in the number of fecal pellets as well as an increase in the amount of wet and dry feces. Interestingly, only CB, at the dose of 100 mg/kg, caused a significant purgative effect. The TDP was also found to affect the amounts of PMA and crotonic acid. While the amount of PMA in C. tiglium seed powder decreased from 1.59 mg/g in CB to 1.26 mg/g in CA, the amount of crotonic acid decreased from 0.001 mg/g in CB to an undetectable level in CA. This investigation demonstrated that TDP not only reduced the purgative effect and toxicity of croton seeds but also the amounts of PMA and crotonic acid.
Journal Article