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1.
J Med Food ; 27(4): 359-368, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38526569

ABSTRACT

As the body's largest organ, the skin is located at the internal and external environment interface, serving as a line of defense against various harmful stressors. Recently, marine-derived physiologically active ingredients have attracted considerable attention in the cosmeceutical industry due to their beneficial effects on skin health. Sargassum, a genus of brown macroalgae, has traditionally been consumed as food and medicine in several countries and is rich in bioactive compounds such as meroterpenoids, sulfated polysaccharides, fucoidan, fucoxanthin, flavonoids, and terpenoids. Sargassum spp. have various beneficial effects on skin disorders. They help with atopic dermatitis by improving skin barrier protection and reducing inflammation. Several species show potential in treating acne by inhibiting bacterial growth and reducing inflammation. Some species, such as Sargassum horneri, demonstrate antiallergic effects by modulating mast cell activity. Certain Sargassum species exhibit anticancer activity by inhibiting tumor growth and promoting apoptosis, and some species help with wound healing by promoting angiogenesis and reducing oxidative stress. Overall, Sargassum spp. demonstrate potential for treating and managing various skin conditions. Therefore, the bioactive compounds of Sargassum spp. may be natural ingredients with a wide range of functional properties for preventing and treating skin disorders. The present review focused on the various biological effects of Sargassum extracts and derived compounds on skin disorders.


Subject(s)
Sargassum , Seaweed , Humans , Skin , Inflammation , Terpenes/pharmacology
2.
Cutis ; 113(1): 22-24, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38478934

ABSTRACT

Azadirachta indica, commonly known as neem, has many uses as a natural remedy. We review and discuss the pharmacologic, biologic, and medicinal properties of neem in disease management. We also report a rare clinical case of a 77-year-old man who presented with a hypopigmented rash on the lower back, bilateral flanks, and buttocks after 6 months of repeated application of neem oil to treat persistent arthritis and lower back pain.


Subject(s)
Azadirachta , Male , Humans , Aged , Glycerides/pharmacology , Terpenes/pharmacology , Plant Extracts
3.
Pol J Vet Sci ; 27(1): 135-138, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38511650

ABSTRACT

The aim of this study was to investigate the antimycobacterial activity of 39 free terpenes and their activity in combination with streptomycin. Antimicrobial activity was first evaluated by screening 39 free terpenes at concentrations from 1.56 to 400 µg/mL. None of these exhibited positive effects against any of the nontuberculous mycobacteria (NTM) strains tested. However, six of the 39 terpenes (isoeugenol, nerol, (+)-α-terpineol, (1R)-(-)-myrtenol, (+)-terpinen-4-ol, and eugenol) were shown to enhance the activity of streptomycin against the NTM strains isolated from diseased ornamental fish.


Subject(s)
Nontuberculous Mycobacteria , Streptomycin , Animals , Streptomycin/pharmacology , Anti-Bacterial Agents/pharmacology , Terpenes/pharmacology , Microbial Sensitivity Tests/veterinary
4.
Biomolecules ; 14(2)2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38397437

ABSTRACT

Cancer has become one of the most multifaceted and widespread illnesses affecting human health, causing substantial mortality at an alarming rate. After cardiovascular problems, the condition has a high occurrence rate and ranks second in terms of mortality. The development of new drugs has been facilitated by increased research and a deeper understanding of the mechanisms behind the emergence and advancement of the disease. Numerous preclinical and clinical studies have repeatedly demonstrated the protective effects of natural terpenoids against a range of malignancies. Numerous potential bioactive terpenoids have been investigated in natural sources for their chemopreventive and chemoprotective properties. In practically all body cells, the signaling molecule referred to as signal transducer and activator of transcription 3 (STAT3) is widely expressed. Numerous studies have demonstrated that STAT3 regulates its downstream target genes, including Bcl-2, Bcl-xL, cyclin D1, c-Myc, and survivin, to promote the growth of cells, differentiation, cell cycle progression, angiogenesis, and immune suppression in addition to chemotherapy resistance. Researchers viewed STAT3 as a primary target for cancer therapy because of its crucial involvement in cancer formation. This therapy primarily focuses on directly and indirectly preventing the expression of STAT3 in tumor cells. By explicitly targeting STAT3 in both in vitro and in vivo settings, it has been possible to explain the protective effect of terpenoids against malignant cells. In this study, we provide a complete overview of STAT3 signal transduction processes, the involvement of STAT3 in carcinogenesis, and mechanisms related to STAT3 persistent activation. The article also thoroughly summarizes the inhibition of STAT3 signaling by certain terpenoid phytochemicals, which have demonstrated strong efficacy in several preclinical cancer models.


Subject(s)
Neoplasms , STAT3 Transcription Factor , Humans , Apoptosis , Cell Proliferation , Neoplasms/drug therapy , Plant Extracts/pharmacology , Signal Transduction , STAT3 Transcription Factor/metabolism , Terpenes/pharmacology
5.
PLoS One ; 19(2): e0293124, 2024.
Article in English | MEDLINE | ID: mdl-38324615

ABSTRACT

The development of insecticide resistance in mosquitoes of public health importance has encouraged extensive research into innovative vector control methods. Terpenes are the largest among Plants Secondary Metabolites and have been increasingly studied for their potential as insecticidal control agents. Although promising, terpenes are insoluble in water, and they show low residual life which limits their application for vector control. In this study, we developed and evaluated the performances of terpenoid-based nanoemulsions (TNEs) containing myrcene and p-cymene against the dengue vector Aedes aegypti and investigated their potential toxicity against non-target organisms. Our results showed that myrcene and p-cymene showed moderate larvicidal activity against mosquito larvae compared to temephos an organophosphate widely used for mosquito control. However, we showed similar efficacy of TNEs against both susceptible and highly insecticide-resistant mosquitoes from French Guyana, hence suggesting an absence of cross-resistance with conventional insecticides. We also showed that TNEs remained effective for up to 45 days in laboratory conditions. The exposure of zebrafish to TNEs triggered behavioral changes in the fish at high doses but they did not alter the normal functioning of zebrafish organs, suggesting a good tolerability of non-target organisms to these molecules. Overall, this study provides new insights into the insecticidal properties and toxicity of terpenes and terpenoid-based formulations and confirms that TNE may offer interesting prospects for mosquito control as part of integrated vector management.


Subject(s)
Acyclic Monoterpenes , Aedes , Alkenes , Cymenes , Dengue , Insecticides , Animals , Terpenes/pharmacology , Zebrafish , Mosquito Vectors , Insecticides/pharmacology , Dengue/prevention & control , Larva
6.
Article in English | MEDLINE | ID: mdl-38417478

ABSTRACT

BACKGROUND: The cannabis plant contains several cannabinoids, and many terpenoids that give cannabis its distinctive flavoring and aroma. Δ9-Tetrahydrocannabinol (Δ9-THC) is the plant's primary psychoactive constituent. Given the abuse liability of Δ9-THC, assessment of the psychoactive effects of minor cannabinoids and other plant constituents is important, especially for compounds that may be used medicinally. This study sought to evaluate select minor cannabinoids and terpenes for Δ9-THC-like psychoactivity in mouse Δ9-THC drug discrimination and determine their binding affinities at CB1 and CB2 receptors. METHODS: Δ9-THC, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), cannabichromenevarin (CBCV), Δ8-tetrahydrocannabinol (Δ8-THC), (6aR,9R)-Δ10-tetrahydrocannabinol [(6aR,9R)-Δ10-THC], Δ9-tetrahydrocannabinol varin (THCV), ß-caryophyllene (BC), and ß-caryophyllene oxide (BCO) were examined. RESULTS: All minor cannabinoids showed measurable cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor binding, with CBC, CBCV, and CBD, showing the weakest CB1 receptor binding affinity. BC and BCO exhibited negligible affinity for both CB1 and CB2 receptors. In drug discrimination, only Δ8-THC fully substituted for Δ9-THC, while CBN and (6aR,9R)-Δ10-THC partially substituted for Δ9-THC. THCV and BCO did not alter the discriminative stimulus effects of Δ9-THC. CONCLUSION: In summary, only some of myriad cannabinoids and other chemicals found in the cannabis plant bind potently to the identified cannabinoid receptors. Further, only four of the compounds tested herein [Δ9-THC, Δ8-THC, (6aR,9R)-Δ10-THC, and CBN] produced Δ9-THC-like discriminative stimulus effects, suggesting they may possess cannabimimetic subjective effects. Given that the medicinal properties of phytocannabinoids and terpenoids are being investigated scientifically, delineation of their potential adverse effects, including their ability to produce Δ9-THC-like intoxication, is crucial.


Subject(s)
Cannabidiol , Cannabinoids , Cannabis , Mice , Animals , Dronabinol/pharmacology , Terpenes/pharmacology , Cannabinoids/pharmacology , Cannabinoids/metabolism , Cannabis/metabolism , Cannabidiol/pharmacology , Cannabinol/pharmacology
7.
Vet Parasitol ; 327: 110149, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38412588

ABSTRACT

The tick Rhipicephalus microplus is a parasite of great importance in cattle breeding. It is responsible for huge economic losses. The application of synthetic acaricides is used as a form of control. However, resistant strains have been selected over the years, making it necessary to search for new alternative formulations. The present study aimed to formulate biodegradable films impregnated with the terpenes carvacrol and thymol and evaluate their efficacy on larvae and adults of R. microplus through in vitro tests. The following formulations were prepared: Film 1 (starch based); Film 2 (based on starch and glycerol); Film 1 + Carvarcol or Thymol; Film 2 + Carvarcol or Thymol. Terpenes had a final concentration of 5.0 mg/mL. To evaluate the formulations on larvae, the immersion test was performed by dividing into six groups according to the concentration of terpenes: 5.0, 2.5, 1.25, 0.625, 0.313, 0.156 mg/mL and the control groups: 1% ethanol solution; 10% ethanol solution; Film 1; and Film 2. For the evaluations on adult ticks, ten experimental groups (n = 10) were used: 1) Carvacrol; 2) Film 1 + Carvacrol; 3) Film 2 + Carvacrol; 4) Thymol; 5) Film 1 + Thymol; 6) Film 2 + Thymol; 7) Distilled water; 8) 10% ethanol solution; 9) Film 1; and 10) Film 2. In experimental groups 1-6, carvacrol and thymol (free or incorporated in two different biodegradable film formulations) were evaluated at the same concentration (5.0 mg/mL). Each group of ticks was immersed in their respective solutions for five minutes. The results of the tests on larvae showed that the Film 1 + thymol and Film 2 + carvacrol formulations had the lowest lethal concentrations (0.076 and 0.255 mg/mL, respectively), values up to 9.0-fold lower than the monoterpenes tested outside the formulation. Carvacrol and thymol at the concentrations tested were effective in controlling engorged females with a percentage of 32.2% and 63.8%, respectively. When incorporated into biodegradable film formulations, these monoterpenes showed much greater efficacy. Film 1 + carvacrol and Film 2 + carvacrol with control percentages of 71.6% and 97.2%, respectively, while the formulations Film 1 + thymol and Film 2 + thymol showed values of 96.9% and 100.0%. The tick control activity of the biopolymer formulations with thymol and carvacrol was demonstrated through the high mortality rates of larvae and engorged females of the tick R. microplus. Therefore, the results obtained indicate that these formulations have great potential for tick control mainly because of the percentage of control up to 100% in engorged females in in vitro tests.


Subject(s)
Acaricides , Cymenes , Rhipicephalus , Female , Animals , Cattle , Thymol/pharmacology , Terpenes/pharmacology , Zea mays , Starch/pharmacology , Plant Breeding , Monoterpenes/pharmacology , Acaricides/pharmacology , Ethanol/pharmacology , Larva
8.
J Nat Prod ; 87(2): 358-364, 2024 02 23.
Article in English | MEDLINE | ID: mdl-38320400

ABSTRACT

Bioassay-guided isolation of the extract from the marine sponge Diacarnus spinipoculum showing inhibitory activity against human transient receptor potential ankyrin 1 (hTRPA1) resulted in the isolation of 12 norditerpene cyclic peroxides (1-12) and eight norsesterterpene cyclic peroxides (13-20). Among these, 10 (5-7, 11, 12, 16-20) are unprecedented analogs. Compounds with either a hydroxy (5, 11) or a methoxy (6, 12) group attached to the cyclohexanone moiety were obtained as epimeric mixtures at C-11, while compounds 4, 6, 10, and 12 are likely the artifacts of isolation. The absolute configurations of the new compounds were established based on an NMR-based empirical method and comparison of specific rotation values. Mosher ester analysis revealed the absolute configurations of compounds 17-20. The inhibitory activity of the isolated compounds against hTRPA1 varied significantly depending on their structures, with the norsesterterpenoid 19 displaying the most potent activity (IC50 2.0 µM).


Subject(s)
Diterpenes , Porifera , Animals , Humans , Ankyrins/antagonists & inhibitors , Molecular Structure , Peroxides/pharmacology , Peroxides/chemistry , Porifera/chemistry , Terpenes/pharmacology , Terpenes/chemistry
9.
Res Vet Sci ; 169: 105174, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38340381

ABSTRACT

Statins are inhibitors of the mevalonic acid pathway that mediates cellular metabolism by producing cholesterol and isoprenoids and are widely used in treating hypercholesterolaemia in humans. Lipophilic statins, including simvastatin, induce death in various tumour cells. However, the cytotoxic mechanisms of statins in tumour cells remain largely unexplored. This study aimed to elucidate the cytotoxic mechanisms of simvastatin in canine lymphoma cells. Simvastatin induced cell death via c-Jun N-terminal kinase (JNK) activation and autophagy in canine T-cell lymphoma cell lines Ema and UL-1, but not in B-cell lines. Cell death was mediated by induction of caspase-dependent apoptosis in UL-1 cells, but not in Ema cells. Blockade of autophagy by lysosomal inhibitors attenuated simvastatin-induced JNK activation and cell death. Isoprenoids, including farnesyl pyrophosphate and geranylgeranyl pyrophosphate, attenuated simvastatin-induced autophagy, JNK activation, and cell death. In UL-1 cells, simvastatin treatment resulted in the cell cycle arrest at the G2/M phase, which was altered to G0/1 phase cell cycle arrest by treatment with lysosomal inhibitors. These findings demonstrate that depletion of isoprenoids by simvastatin induces autophagy-mediated cell death via downstream JNK activation and cell cycle dysregulation in canine T-cell lymphoma cells.


Subject(s)
Antineoplastic Agents , Dog Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Lymphoma, T-Cell , Animals , Dogs , Humans , Simvastatin/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , JNK Mitogen-Activated Protein Kinases/metabolism , Cell Line, Tumor , Cell Cycle , Cell Division , Apoptosis , Cell Death , Antineoplastic Agents/pharmacology , Autophagy , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/veterinary , Terpenes/pharmacology , Dog Diseases/drug therapy
10.
Chem Biodivers ; 21(4): e202301431, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38363027

ABSTRACT

Terpene-derived alkaloids show a variety of biological activities, including antioxidant, anti-inflammatory, antimicrobial and cytotoxicity effects. In this work, homologated monoterpene amines have been prepared via a rhodium-catalyzed hydroaminomethylation of biomass-based alkenes, such as (R)-limonene, linalool, myrcene and camphene, in combination with secondary amines of aliphatic and aromatic nature, namely morpholine and N-methylaniline, leading to highly chemo- and regioselective processes. The as-prepared amines were obtained in 50-99 % overall yields, and in vitro tested on a human colon cancer cell line (HCT-116) to evaluate their cytotoxic potential. The lead compound of the series (3 a) showed cytotoxicity in the micromolar range (IC50 52.46 µM) via the induction of cell death by apoptosis, paving the way towards further structure-activity relationship studies.


Subject(s)
Amines , Rhodium , Humans , Amines/pharmacology , Terpenes/pharmacology , Molecular Structure , Catalysis
11.
Molecules ; 29(2)2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38257323

ABSTRACT

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds-cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis's bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis's sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis's complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis's full therapeutic potential within the realm of natural plant-based medicine.


Subject(s)
Cannabidiol , Cannabis , Hallucinogens , Neuroinflammatory Diseases , Terpenes/pharmacology , Cannabinoid Receptor Agonists , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Flavonoids/pharmacology , Flavonoids/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
12.
PLoS Pathog ; 20(1): e1011557, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38277417

ABSTRACT

A proposed treatment for malaria is a combination of fosmidomycin and clindamycin. Both compounds inhibit the methylerythritol 4-phosphate (MEP) pathway, the parasitic source of farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively). Both FPP and GGPP are crucial for the biosynthesis of several essential metabolites such as ubiquinone and dolichol, as well as for protein prenylation. Dietary prenols, such as farnesol (FOH) and geranylgeraniol (GGOH), can rescue parasites from MEP inhibitors, suggesting the existence of a missing pathway for prenol salvage via phosphorylation. In this study, we identified a gene in the genome of P. falciparum, encoding a transmembrane prenol kinase (PolK) involved in the salvage of FOH and GGOH. The enzyme was expressed in Saccharomyces cerevisiae, and its FOH/GGOH kinase activities were experimentally validated. Furthermore, conditional knockout parasites (Δ-PolK) were created to investigate the biological importance of the FOH/GGOH salvage pathway. Δ-PolK parasites were viable but displayed increased susceptibility to fosmidomycin. Their sensitivity to MEP inhibitors could not be rescued by adding prenols. Additionally, Δ-PolK parasites lost their capability to utilize prenols for protein prenylation. Experiments using culture medium supplemented with whole/delipidated human plasma in transgenic parasites revealed that human plasma has components that can diminish the effectiveness of fosmidomycin. Mass spectrometry tests indicated that both bovine supplements used in culture and human plasma contain GGOH. These findings suggest that the FOH/GGOH salvage pathway might offer an alternate source of isoprenoids for malaria parasites when de novo biosynthesis is inhibited. This study also identifies a novel kind of enzyme related to isoprenoid metabolism.


Subject(s)
Diterpenes , Fosfomycin/analogs & derivatives , Hemiterpenes , Parasites , Pentanols , Humans , Animals , Cattle , Parasites/metabolism , Phosphates , Terpenes/pharmacology , Terpenes/metabolism
13.
Mar Pollut Bull ; 199: 116023, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38211540

ABSTRACT

This comprehensive review examines the diverse classes of pharmacologically active compounds found in marine algae and their promising anti-inflammatory effects. The review covers various classes of anti-inflammatory compounds sourced from marine algae, including phenolic compounds, flavonoids, terpenoids, caretenoids, alkaloids, phlorotannins, bromophenols, amino acids, peptides, proteins, polysaccharides, and fatty acids. The anti-inflammatory activities of marine algae-derived compounds have been extensively investigated using in vitro and in vivo models, demonstrating their ability to inhibit pro-inflammatory mediators, such as cytokines, chemokines, and enzymes involved in inflammation. Moreover, marine algae-derived compounds have exhibited immunomodulatory properties, regulating immune cell functions and attenuating inflammatory responses. Specific examples of compounds with notable anti-inflammatory activities are highlighted. This review provides valuable insights for researchers in the field of marine anti-inflammatory pharmacology and emphasizes the need for further research to harness the pharmacological benefits of marine algae-derived compounds for the development of effective and safe therapeutic agents.


Subject(s)
Anti-Inflammatory Agents , Terpenes , Humans , Anti-Inflammatory Agents/pharmacology , Terpenes/pharmacology , Inflammation , Polysaccharides
14.
Bioorg Chem ; 143: 107073, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176375

ABSTRACT

Six new highly oxygenated and polycyclic andrastin-type meroterpenoids, namely, bialorastins A-F (1-6), were discovered from the culture of Penicillium bialowiezense CS-283, a fungus isolated from the deep-sea cold seep squat lobster Shinkaia crosnieri. The planar structures and absolute configurations of these compounds were determined by detailed analysis of spectroscopic data, single crystal X-ray diffraction, and TDDFT-ECD calculations. Structurally, bialorastin A (1) represents a rare 17-nor-andrastin that possesses an unusual 2-oxaspiro[4.5]decane-1,4-dione moiety with a unique 6/6/6/6/5 polycyclic system, while bialorastin B (2) is also a 17-nor-andrastin featuring a gem-propane-1,2-dione moiety. Additionally, bialorastins C-E (3-5) possess a 6/6/6/6/5/5 fused hexacyclic skeleton, characterized by distinctive 3,23-acetal/lactone-bridged functionalities. All isolated compounds were evaluated for their proangiogenic activities in transgenic zebrafish. Compound 3 exhibited significant proangiogenic activity, which notably increased the number and length of intersegmental blood vessels in model zebrafish in a dose-dependent manner at concentrations of 20 and 40 µM. On a molecular scale, the tested compounds were modeled through molecular docking to have insight into the interactions with the possible target VEGFR2. Mechanistically, RT-qPCR results revealed that compound 3 could promote angiogenesis via activating VEGFR2 and subsequently activating the downstream PI3K/AKT and MAPK signaling pathways. These findings indicate that 3 could be a potential lead compound for developing angiogenesis agents.


Subject(s)
Penicillium , Terpenes , Zebrafish , Animals , Fungi , Molecular Docking Simulation , Molecular Structure , Penicillium/chemistry , Phosphatidylinositol 3-Kinases , Terpenes/chemistry , Terpenes/pharmacology
15.
Med Res Rev ; 44(3): 1221-1266, 2024 May.
Article in English | MEDLINE | ID: mdl-38204140

ABSTRACT

Ganoderma meroterpenoids (GMs) containing 688 structures to date were discovered to have multiple remarkable biological activities. 65.6% of meroterpenoids featuring stereogenic centers from Ganoderma species are racemates. Further, GMs from different Ganoderma species seem to have their own characteristics. In this review, a comprehensive summarization of GMs since 2000 is presented, including GM structures, structure corrections, biological activities, physicochemical properties, total synthesis, and proposed biosynthetic pathways. Additionally, we especially discuss the racemic nature, species-related structural distribution, and structure-activity relationship of GMs, which will provide a likely in-house database and shed light on future studies on GMs.


Subject(s)
Agaricales , Biological Products , Ganoderma , Humans , Terpenes/pharmacology , Terpenes/chemistry , Ganoderma/chemistry , Biological Products/pharmacology , Molecular Structure
16.
J Agric Food Chem ; 72(2): 956-972, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38189231

ABSTRACT

Petroselinum crispum (Mill.) Fuss (parsley) is a popular medicinal plant widely used in different traditional medicines all over the world. This paper provides an updated review on the traditional use, phytochemistry, and pharmacological activities of parsley. Parsley contains volatile compounds such as terpenes and terpenoids in the essential oil, as well as phenolic compounds in the plant extract. Parsley is traditionally used as a diuretic, liver and stomach tonic, and for urolithiasis and indigestion. Pharmacological investigations also confirm several biological activities of parsley including hepatoprotective, nephroprotective, antiurolithiatic, neuroprotective, cardioprotective, and antineoplastic effects in animal and cell-based studies. Parsley has currently demonstrated several pharmacological activities in preclinical studies; however, there is a big lack in clinical evidence. Considering parsley as a possible valuable medicinal food, future clinical trials are recommended to evaluate the clinical efficacy and safety of the plant in different health conditions.


Subject(s)
Oils, Volatile , Petroselinum , Animals , Petroselinum/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Liver , Terpenes/pharmacology
17.
J Biomol Struct Dyn ; 42(2): 1072-1078, 2024.
Article in English | MEDLINE | ID: mdl-37139540

ABSTRACT

Coronavirus, an extremely contagious infections disease had a harmful effect on the world's population. It is a family of enveloped, single-stranded, positive-strand RNA viruses of Nidovirales order belongs to coroviridae family. At present, worldwide several lakhs of deaths and several billions of infections have been reported. Hence, the focus of the present study was to assess the SARS-CoV-2 enzyme inhibitory potential of certain commercially available terpenoids using Lamarckian genetic algorithm as a working principle and molecular dynamic studies was also performed. AutoDock 4.2 software was used to perform the computational docking calculations of terpenoids against SARS-CoV-2 enzyme. The terpenoids such as, Andrographolide, Betulonic acid, Erythrodiol, Friedelin, Mimuscopic acid, Moronic acid, and Retinol were selected based on the drug likeness properties. Remdesivir a well-known anti-viral drug was selected as the standard drug. Molecular dynamic simulation studies were carried using Desmond module of Schrodinger Suite. In the current study we observed that, Friedelin was exhibited excellent SARS-CoV-2 enzyme inhibitory potential than the standard drug and other selected terpenoids. Friedelin and the standard Remdesivir was undergone the molecular dynamic studies and Friedelin showed a good number of hydrogen bonds over the simulation time of 100 ns. Based on the in silico computational evaluation, it can be concluded that Friedelin could be worthwhile terpenoid against SARS-CoV-2 spike protein. A further study on Friedelin is required to develop a potential chemical entity against the management of COVID disease.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Lupanes , Triterpenes , Humans , Terpenes/pharmacology , Spike Glycoprotein, Coronavirus , SARS-CoV-2 , Molecular Dynamics Simulation , Glycoproteins , Molecular Docking Simulation , Protease Inhibitors
18.
J Biomol Struct Dyn ; 42(4): 1966-1984, 2024.
Article in English | MEDLINE | ID: mdl-37173829

ABSTRACT

Bacterial infections are rising, and antimicrobial resistance (AMR) in bacteria has worsened the scenario, requiring extensive research to find alternative therapeutic agents. Terpenoids play an essential role in protecting plants from herbivores and pathogens. The present study was designed to focus on in silico evaluation of terpenoids for their affinity towards two necessary enzymes, i.e. DHFR and DHPS, which are involved in forming 5, 6, 7, 8-tetrahydrofolate, a key component in bacterial DNA synthesis proteins. Additionally, to account for activity against resistant bacteria, their affinity towards the L28R mutant of DHFR was also assessed in the study. The structure-based drug design approach was used to screen the compound library of terpenes for their interaction with active sites of DHFR and DHPS. Further, compounds were screened based on their dock score, pharmacokinetic properties, and binding affinities. A total of five compounds for each target protein were screened, having dock scores better than their respective standard drug molecules. CNP0169378 (-8.4 kcal/mol) and CNP0309455 (-6.5 kcal/mol) have been identified as molecules with a higher affinity toward the targets of DHFR and DHPS, respectively. At the same time, one molecule CNP0298407 (-5.8 kcal/mol for DHPS, -7.6 kcal/mol for DHFR, -6.1 kcal/mol for the L28R variant), has affinity for both proteins (6XG5 and 6XG4). All the molecules have good pharmacokinetic properties. We further validated the docking study by binding free energy calculations using the MM/GBSA approach and molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.


Subject(s)
Antimalarials , Folic Acid Antagonists , Antimalarials/pharmacology , Pyrimethamine , Folic Acid Antagonists/pharmacology , Sulfadoxine/pharmacology , Sulfadoxine/therapeutic use , Molecular Dynamics Simulation , Dihydropteroate Synthase/genetics , Terpenes/pharmacology , Plasmodium falciparum , Tetrahydrofolate Dehydrogenase/genetics
19.
J Biomol Struct Dyn ; 42(3): 1404-1416, 2024.
Article in English | MEDLINE | ID: mdl-37066614

ABSTRACT

The misuse and overuse of antibiotics have resulted in antibiotic resistance. However, there are alternative approaches that could either substitute antibiotics or enhance their effectiveness without harmful side effects. One such approach is the use of terpene-rich essential oils. In this study, we aimed to demonstrate the antibacterial activity of the main components of three plant essential oils, namely Anthemis punctata, Anthemis pedunculata and Daucus crinitus. Specifically, we targeted bacterial tyrosyl-tRNA synthetase, an enzyme that plays a critical role in bacterial protein synthesis. To investigate how the phytocompounds interact with the enzyme's active sites, we employed a molecular docking study using Autodock Software Tools 1.5.7. Our findings revealed that all 28 phytocompounds bound to the enzyme's active sites with binding energies ranging from -6.96 to -4.03 kcal/mol. These results suggest that terpene-rich essential oils could be a potential source of novel antimicrobial agents.Communicated by Ramaswamy H. Sarma.


Subject(s)
Oils, Volatile , Tyrosine-tRNA Ligase , Tyrosine-tRNA Ligase/metabolism , Molecular Docking Simulation , Oils, Volatile/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Terpenes/pharmacology
20.
Phytother Res ; 38(2): 636-645, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37963759

ABSTRACT

Hyperforin is a phloroglucinol derivative isolated from the medicinal plant Hypericum perforatum (St John's wort, SJW). This lipophilic biomolecule displays antibacterial, pro-apoptotic, antiproliferative, and anti-inflammatory activities. In addition, in vitro and in vivo data showed that hyperforin is a promising molecule with potential applications in neurology and psychiatry. For instance, hyperforin possesses antidepressant properties, impairs the uptake of neurotransmitters, and stimulates the brain derived neurotrophic factor (BDNF)/TrkB neurotrophic signaling pathway, the adult hippocampal neurogenesis, and the brain homeostasis of zinc. In fact, hyperforin is a multi-target biomolecule with a complex neuropharmacological profile. However, one prominent pharmacological feature of hyperforin is its ability to influence the homeostasis of cations such as Ca2+ , Na+ , Zn2+ , and H+ . So far, the pathophysiological relevance of these actions is currently unknown. The main objective of the present work is to provide an overview of the cellular neurobiology of hyperforin, with a special focus on its effects on neuronal membranes and the movement of cations.


Subject(s)
Hypericum , Neurobiology , Phloroglucinol/analogs & derivatives , Antidepressive Agents/pharmacology , Terpenes/pharmacology , Phloroglucinol/pharmacology , Plant Extracts/pharmacology , Cations , Bridged Bicyclo Compounds/pharmacology
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