Mitochondrial sirtuin 3 and role of natural compounds: the effect of post-translational modifications on cellular metabolism.

Sirtuins (SIRTs) are a family of proteins with enzymatic activity. In particular, they are a family of class III NAD+-dependent histone deacetylases and ADP-ribosyltransferases. NAD+-dependent deac(et)ylase activities catalyzed by sirtuin include ac(et)ylation, propionylation, butyrylation, crotonylation, manylation, and succinylation. Specifically, human SIRT3 is a 399 amino acid protein with two functional domains: a large Rossmann folding motif and NAD+ binding, and a small complex helix and zinc-binding motif. SIRT3 is widely expressed in mitochondria-rich tissues and is involved in maintaining mitochondrial integrity, homeostasis, and function. Moreover, SIRT3 regulates related diseases, such as aging, hepatic, kidney, neurodegenerative and cardiovascular disease, metabolic diseases, and cancer development. In particular, one of the most significant and damaging post-translational modifications is irreversible protein oxidation, i.e. carbonylation. This process is induced explicitly by increased ROS production due to mitochondrial dysfunction. SIRT3 is carbonylated by 4-hydroxynonenal at the level of Cys280. The carbonylation induces conformational changes in the active site, resulting in allosteric inhibition of SIRT3 activity and loss of the ability to deacetylate and regulate antioxidant enzyme activity. Phytochemicals and, in particular, polyphenols, thanks to their strong antioxidant activity, are natural compounds with a positive regulatory action on SIRT3 in various pathologies. Indeed, the enzymatic SIRT3 activity is modulated, for example, by different natural polyphenol classes, including resveratrol and the bergamot polyphenolic fraction. Thus, this review aims to elucidate the mechanisms by which phytochemicals can interact with SIRT3, resulting in post-translational modifications that regulate cellular metabolism.

The evolution of chemodiversity in plants-From verbal to quantitative models.

Plants harbour a great chemodiversity, that is diversity of specialised metabolites (SMs), at different scales. For instance, individuals can produce a large number of SMs, and populations can differ in their metabolite composition. Given the ecological and economic importance of plant chemodiversity, it is important to understand how it arises and is maintained over evolutionary time. For other dimensions of biodiversity, that is species diversity and genetic diversity, quantitative models play an important role in addressing such questions. Here, we provide a synthesis of existing hypotheses and quantitative models, that is mathematical models and computer simulations, for the evolution of plant chemodiversity. We describe each model's ingredients, that is the biological processes that shape chemodiversity, the scales it considers and whether it has been formalized as a quantitative model. Although we identify several quantitative models, not all are dynamic and many influential models have remained verbal. To fill these gaps, we outline our vision for the future of chemodiversity modelling. We identify quantitative models used for genetic variation that may be adapted for chemodiversity, and we present a flexible framework for the creation of individual-based models that address different scales of chemodiversity and combine different ingredients that bring this chemodiversity about.

Mitigation of cadmium-induced stress in maize via synergistic application of biochar and gibberellic acid to enhance morpho-physiological and biochemical traits.

Cadmium (Cd), being a heavy metal, tends to accumulate in soils primarily through industrial activities, agricultural practices, and atmospheric deposition. Maize, being a staple crop for many regions, is particularly vulnerable to Cd contamination, leading to compromised growth, reduced yields, and potential health risks for consumers. Biochar (BC), a carbon-rich material derived from the pyrolysis of organic matter has been shown to improve soil structure, nutrient retention and microbial activity. The choice of biochar as an ameliorative agent stems from its well-documented capacity to enhance soil quality and mitigate heavy metal stress. The study aims to contribute to the understanding of the efficacy of biochar in combination with GA3, a plant growth regulator known for its role in promoting various physiological processes, in mitigating the adverse effects of Cd stress. The detailed investigation into morpho-physiological attributes and biochemical responses under controlled laboratory conditions provides valuable insights into the potential benefits of these interventions. The experimental design consisted of three replicates in a complete randomized design (CRD), wherein soil, each containing 10 kg was subjected to varying concentrations of cadmium (0, 8 and 16 mg/kg) and biochar (0.75% w/w base). Twelve different treatment combinations were applied, involving the cultivation of 36 maize plants in soil contaminated with Cd (T1: Control (No Cd stress; T2: Mild Cd stress (8 mg Cd/kg soil); T3: Severe Cd stress (16 mg Cd/kg soil); T4: 10 ppm GA3 (No Cd stress); T5: 10 ppm GA3 + Mild Cd stress; T6: 10 ppm GA3 + Severe Cd stress; T7: 0.75% Biochar (No Cd stress); T8: 0.75% Biochar + Mild Cd stress; T9: 0.75% Biochar + Severe Cd stress; T10: 10 ppm GA3 + 0.75% Biochar (No Cd stress); T11: 10 ppm GA3 + 0.75% Biochar + Mild Cd stress; T12: 10 ppm GA3 + 0.75% Biochar + Severe Cd stress). The combined application of GA3 and BC significantly enhanced multiple parameters including germination (27.83%), root length (59.53%), shoot length (20.49%), leaf protein (121.53%), root protein (99.93%), shoot protein (33.65%), leaf phenolics (47.90%), root phenolics (25.82%), shoot phenolics (25.85%), leaf chlorophyll a (57.03%), leaf chlorophyll b (23.19%), total chlorophyll (43.77%), leaf malondialdehyde (125.07%), root malondialdehyde (78.03%) and shoot malondialdehyde (131.16%) across various Cd levels compared to the control group. The synergistic effect of GA3 and BC manifested in optimal leaf protein and malondialdehyde levels indicating induced tolerance and mitigation of Cd detrimental impact on plant growth. The enriched soils showed resistance to heavy metal toxicity emphasizing the potential of BC and GA3 as viable strategy for enhancing maize growth. The application of biochar and gibberellic acid emerges as an effective means to mitigate cadmium-induced stress in maize, presenting a promising avenue for sustainable agricultural practices.

Major quality regulation network of flavonoid synthesis governing the bioactivity of black wolfberry.

Black wolfberry (Lycium ruthenicum Murr.) contains various bioactive metabolites represented by flavonoids, which are quite different among production regions. However, the underlying regulation mechanism of flavonoid biosynthesis governing the bioactivity of black wolfberry remains unclear. Presently, we compared the bioactivity of black wolfberry from five production regions. Multi-omics were performed to construct the regulation network associated with the fruit bioactivity. The detailed regulation mechanisms were identified using genetic and molecular methods. Typically, Qinghai (QH) fruit exhibited higher antioxidant and anti-inflammatory activities. The higher medicinal activity of QH fruit was closely associated with the accumulation of eight flavonoids, especially Kaempferol-3-O-rutinoside (K3R) and Quercetin-3-O-rutinoside (rutin). Flavonoid biosynthesis was found to be more active in QH fruit, and the upregulation of LrFLS, LrCHS, LrF3H and LrCYP75B1 caused the accumulation of K3R and rutin, leading to high medicinal bioactivities of black wolfberry. Importantly, transcription factor LrMYB94 was found to regulate LrFLS, LrCHS and LrF3H, while LrWRKY32 directly triggered LrCYP75B1 expression. Moreover, LrMYB94 interacted with LrWRKY32 to promote LrWRKY32-regulated LrCYP75B1 expression and rutin synthesis in black wolfberry. Transgenic black wolfberry overexpressing LrMYB94/LrWRKY32 contained higher levels of K3R and rutin, and exhibited high medicinal bioactivities. Importantly, the LrMYB94/LrWRKY32-regulated flavonoid biosynthesis was light-responsive, showing the importance of light intensity for the medicinal quality of black wolfberry. Overall, our results elucidated the regulation mechanisms of K3R and rutin synthesis, providing the basis for the genetic breeding of high-quality black wolfberry.

How does plant chemodiversity evolve? Testing five hypotheses in one population genetic model.

Plant chemodiversity, the diversity of plant-specialized metabolites, is an important dimension of biodiversity. However, there are so far few mathematical models to test verbal hypotheses on how chemodiversity evolved. Here, we develop such a model to test predictions of five hypotheses: the 'fluctuating selection hypothesis', the 'dominance reversal hypothesis', the interaction diversity hypothesis, the synergy hypothesis, and the screening hypothesis. We build a population genetic model of a plant population attacked by herbivore species whose occurrence fluctuates over time. We study the model using mathematical analysis and individual-based simulations. As predicted by the 'dominance reversal hypothesis', chemodiversity can be maintained if alleles conferring a defense metabolite are dominant with respect to the benefits, but recessive with respect to costs. However, even smaller changes in dominance can maintain polymorphism. Moreover, our results underpin and elaborate predictions of the synergy and interaction diversity hypotheses, and, to the extent that our model can address it, the screening hypotheses. By contrast, we found only partial support for the 'fluctuating selection hypothesis'. In summary, we have developed a flexible model and tested various verbal models for the evolution of chemodiversity. Next, more mechanistic models are needed that explicitly consider the organization of metabolic pathways.

GC-MS analysis and antifungal potential of flower extract of Acacia nilotica subsp. Indica against Macrophomina phaseolina.

Macrophomina phaseolina is a wide host ranged soil-borne fungal plant pathogen. It infects more than 500 host plant species belonging to 100 families. Many important oil-seed and leguminous crops are known to be attacked by this devastating plant pathogen. In the present study, antifungal potential of flowers of a leguminous tree Acacia nilotica subsp. indica, was assessed against this pathogen through bioassays guided fractionation. Initially, methanolic extracts of 1 %-5 % of leaf, flower, root-bark and stem-bark of the plant species under consideration were evaluated for their antifungal potential against the target pathogen. Among these, the best antifungal activity was shown by flower extract. The reduction in growth of the test fungal strain was 27-49 %, 4-40 % and 2-27 % due to flower, root-bark and leaf extracts, respectivey, over control. Flower extract was partitioned using n-hexane, chloroform, ethyl acetate and n-butanol as the solvents. Bioassays guided study of these fractions of methanolic extract of flower revealed that high antifungal potential was shown by n-hexane and chloroform fractions against M. phaseolina causing 26-53 % and 28-50 % decline in fungal biomass, respectively, as compared to that of control. GC-MS analysis of chloroform fraction revealed the presence of 27 compounds in this fraction. Among these cyclopentanol,-1-methyl (10.93 %) was the predominant compound followed by methyl, 4,4-dimethyl butanoate (7.04 %), 1-pentanol (6.80 %), 2-propanol, 1-cyclopropyl (6.11 %), 1H,imidazole-4-5-dihydro-2-methyl (5.93 %), trichloroethane (5.91 %), carbonic acid-ethyl hexyl ester (4.59 %), 1,4-butandiol,2,3-bis(methylene)- (4.54 %) and [S]-3,4-dimethyl pentanol (4.48 %).

Cellular ROS tolerance determines the effect of plumbagin on osteoclast differentiation.

Plumbagin is used in traditional medicine because of its anti-inflammatory and anti-microbial properties. As a naphthoquinone, plumbagin triggers the production of reactive oxygen species (ROS). In vitro cancer studies showed that plumbagin triggers apoptosis in cancer cells through ROS production. As cancer-mediated chronic inflammation can affect bone density, it was hypothesized that plumbagin might directly inhibit the formation of bone-resorbing osteoclasts. We previously showed that the effect of plumbagin on osteoclastogenesis differed between bone marrow-derived macrophages and the macrophage cell line RAW 264.7. Although RAW 264.7 macrophages are able to initiate the gene program required for osteoclastogenesis, only primary macrophages successfully differentiate into osteoclasts. Here, we show that RAW 264.7 cells are more sensitive toward plumbagin-induced apoptosis. In the presence of plumbagin and the cytokine RANKL, which triggers ROS production to drive osteoclastogenesis, RAW 264.7 macrophages produce increased amounts of ROS and die. Addition of the ROS scavenger N-acetyl cysteine prevented cell death, linking the failure to differentiate to increased ROS levels. RAW 264.7 cells show reduced expression of genes protective against oxidative stress, while primary macrophages have a higher tolerance toward ROS. Our data suggest that it is indispensable to consider cell (line)-intrinsic properties when studying phytochemicals.

Alzheimer, Parkinson, dementia, and phytochemicals: insight review.

Alzheimer's, Parkinson's, and dementia are the leading neurodegenerative diseases that threaten the world with the aging population. Although the pathophysiology of each disease is unique, the steps to be taken to prevent diseases are similar. One of the changes that a person can make alone is to gain the habit of an antioxidant-rich diet. Phytochemicals known for their antioxidant properties have been reported to prevent neurodegenerative diseases in various studies. Phytochemicals with similar chemical structures are grouped. Accordingly, there are two main groups of phytochemicals, flavonoid and non-flavonoid. Various in vitro and in vivo studies on phytochemicals have proven neuroprotective effects by increasing cognitive function with their anti-inflammatory and antioxidant mechanisms. The purpose of this review is to summarize the in vitro and in vivo studies on phytochemicals with neuroprotective effects and to provide insight.

A comprehensive study on Geranium robertianum L. antibacterial potential.

AIMS: The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined. METHODS AND RESULTS: Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml-1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml-1 for ethanol extract, and 958.01 ± 6.14 µg ml-1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts. CONCLUSIONS: The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.

Widespread Production of Polyunsaturated Aldehydes by Benthic Diatoms of the North Pacific Ocean's Salish Sea.

Diatoms are key primary producers across marine, freshwater, and terrestrial ecosystems. They are responsible for photosynthesis and secondary production that, in part, support complex food webs. Diatoms can produce phytochemicals that have transtrophic ecological effects which increase their competitive fitness. Polyunsaturated aldehydes (PUAs) are one class of diatom-derived phytochemicals that are known to have allelopathic and anti-herbivory properties. The anti-herbivory capability of PUAs results from their negative effect on grazer fecundity. Since their discovery, research has focused on their production by pelagic marine diatoms, and their effects on copepod egg production, hatching success, and juvenile survival and development. Few investigations have explored PUA production by the prolific suite of benthic marine diatoms, despite their importance to coastal trophic systems. In this study, we tested eight species of benthic diatoms for the production of the bioactive PUAs 2,4-heptadienal, 2,4-octadienal, and 2,4-decadienal. Benthic diatom species were isolated from the Salish Sea, an inland sea within the North Pacific ecosystem. All species were found to be producers of at least two PUAs in detectable concentrations, with five species producing all three PUAs in quantifiable concentrations. Our results indicate that production of PUAs from Salish Sea benthic diatoms may be widespread, and thus these compounds may contribute to benthic coastal food web dynamics through heretofore unrecognized pathways. Future studies should expand the geographic scope of investigations into benthic diatom PUA production and explore the effects of benthic diatoms on benthic consumer fecundity.

Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice.

Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-ß1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 µM) dose-dependently decreased TGF-ß1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg-1·d-1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.

Comprehensive in vitro evaluation of Indigofera hochstetteri Baker extract: Effect of chemicals in antimicrobial, anticancer, anti-inflammatory, and anti-diabetic activities.

The study aimed to analyze the pharmacological properties of medicinal plant Indigofera hochstetteri Baker extracts. Preliminary phytochemical analysis revealed a diverse range of secondary metabolites present in it. TLC analysis detected numerous phytochemicals with varying Rf values, aiding in different solvent systems. GC-MS analysis revealed the presence of 29 bioactive compounds with diverse pharmacological activities, including anti-inflammatory, antioxidant, analgesic and antimicrobial properties. Antimicrobial effect of I. hochstetteri Baker methanolic extract showed significant inhibitory effects against E. coli, E. aerogenes, S. flexneri, P. aeruginosa, S. aureus, E. faecalis, B. cereus, and fungal strain C. albicans. The methanol extract also showed significant antifungal activity by inhibiting the growth of Sclerotium rolfsii in food poisoning method. MTT assays revealed significant cytotoxic activity of methanolic extract against human leukemia HL-60 cancer cells with IC50 of 116.01 µg/mL. In apoptotic study, I. hochstetteri Baker methanolic extract showed 28.84% viable cells, 30.2% early apoptosis, 35.54% late apoptosis, and 5.86% necrosis comparatively similar with standard used. The extract showed significant anti-inflammatory effect on HRBC stabilization, and protein denaturation of BSA and egg albumin denaturation with IC50 of 193.62 µg/mL, 113.94 µg/mL respectively. In anti-diabetic assays like α-amylase, α-glucosidase, and Glucose uptake assay, I. hochstetteri extract showed good anti-diabetic effect with IC50 of 60.64 µg/mL, 169.34 µg/mL, and 205.63 µg/mL respectively. In conclusion I. hochstetteri Baker have promising bioactive metabolites with significant biological activities, it can be good substitute for the chemical drugs after successful clinical studies.

An Improved Assessment Method to Estimate (Poly)phenol Intake in Adults with Chronic Pancreatitis.

BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped. AIMS: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data. METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample. RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively. CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

Kurarinone targets JAK2-STAT3 signaling in colon cancer-stem-like cells.

Natural compounds are known to regulate stemness/self-renewal properties in colon cancer cells at molecular level. In the present study, we first time studied the colon cancer stem-like cells targeting potential of Kurarinone (KU) and explored the underlying mechanism. Cytotoxic potential of KU was checked in colon cancer cells. Colonosphere formation assay was performed to check the spheroid formation reduction potential of KU in HCT-116 cells by using phase-contrast microscopy. Stemness/self-renewal marker expression was studied at mRNA and protein levels in colonosphere. The qRT-PCR, western blot analysis, and flow cytometer techniques were used to assess the effect of KU treatment on cell cycle progression and apoptosis induction in colon cancer cells and colonosphere. Further, effect of KU treatment on pSTAT3 status and its nuclear translocation was also studied. KU treatment significantly decreased HCT-116 cell proliferation and reduced sphere formation potential at IC30 (8.71 µM) and IC50 (20.34 µM) concentrations compared to respective vehicle-treated groups, respectively. KU exposure significantly reduced the expression of CD44, c-Myc, Bmi-1, and Sox2 stemness/self-renewal markers in colonosphere in a dose-dependent manner. KU treatment inhibits JAK2-STAT3 signaling pathway by reducing pSTAT3 levels and its nuclear translocation in HCT-116 cells and colonosphere at IC50 concentration. KU treatment significantly decreased the expression of CCND1 and CDK4 cell cycle-specific markers and arrested the HCT-116 cells and colonosphere in G1-phase. Further, KU treatment increased Bax/Bcl-2 ratio, apoptotic cell population, cleaved caspase 3, and PARP-1 in HCT-116 cells and colonosphere. In conclusion, KU treatment decreases stemness/self-renewal, induces cell cycle arrest and apoptosis in HCT-116 colonosphere by down-regulating CD44-JAK2-STAT3 axis. Thus, targeting stemness/self-renewal and other cancer hallmark(s) by KU through CD44/JAK2/STAT3 signaling pathway might be a novel strategy to target colon cancer stem-like cells.

The potential causal effect of the pre-pregnancy dietary phytochemical index on gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the pre-pregnancy dietary phytochemical index (DPI) on gestational diabetes mellitus (GDM). METHODS: In this prospective cohort study 1,856 pregnant women aged 18-45 years who were in their first trimester, were recruited and followed up until delivery. The dietary intakes of participants were examined using an interviewer-administered validated 168-item semi-quantitative food frequency questionnaire (FFQ). Inverse probability weighting (IPW) of propensity scores (PS), estimated from the generalized boosted model (GBM) were used to obtain a adjusted risk ratio (aRR) for potential confounders. RESULTS: During the follow-up period, 369 (19.88%) women were diagnosed with GDM. DPI scores ranged from 6.09 to 89.45. There was no association between DPI scores and GDM (aRR: 1.01, 95% confidence interval [CI]: 0.92, 1.08; p trend = 0.922). When comparing DPI quartile 4 (most pro-phytochemical content) to quartile 1 (few phytochemical contents), there was no significant difference between them (aRR: 0.97; 95% CI: 0.75, 1.25; p = 0.852). Also, there was no significant difference between DPI quartile 3 and quartile 1 (aRR: 1.04; 95% CI: 0.81, 1.34; p = 0.741) as well as DPI quartile 2 and quartile 1 (aRR: 0.92; 95% CI: 0.71, 1.21; p = 0.593). CONCLUSIONS: Although this data did not support the association between pre-pregnancy DPI scores and GDM, further cohort studies to ascertain the causal association between them are warranted.

Effect of theanine on the hyperexcitability of trigeminal secondary nociceptive neurons following orofacial inflammation in rats.

The present in vivo study investigated whether systemic administration of theanine attenuates the inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons associated with hyperalgesia. Complete Freund's adjuvant (CFA) was injected into the whisker pads of 24 rats to induce inflammation, and then mechanical stimulation was applied to the orofacial area to assess the threshold of escape. The mechanical threshold was statistically significantly lower in CFA-inflamed rats compared to uninjected naïve rats, and this lowered threshold returned to control levels after 2 days of theanine administration. The mean discharge frequency of SpVc wide-dynamic range (WDR) neurons to mechanical stimuli in anesthetized CFA-inflamed rats was statistically significantly lower after two days of theanine administration. In addition, the increased mean spontaneous discharge of SpVc WDR neurons in CFA-inflamed rats statistically significantly decreased after theanine administration. Similarly, theanine restored the expanded mean receptive field size in CFA-inflamed rats to control levels. Taken together, these results suggest that administration of theanine attenuates inflammatory hyperalgesia associated with hyperexcitability of nociceptive SpVc WDR neurons. These findings support the potential of theanine as a therapeutic agent in complementary alternative medicine strategies to prevent inflammatory hyperalgesia.

The phytochemical plumbagin: mechanism behind its "pleiotropic" nature and potential as an anticancer treatment.

Chemotherapeutics are most often used to treat cancer, but side effects, drug resistance, and toxicity often compromise their effectiveness. In contrast, phytocompound plumbagin possesses a distinct pleiotropic nature, targeting multiple signaling pathways, such as ROS generation, cell death, cellular proliferation, metastasis, and drug resistance, and is shown to enhance the efficacy of chemotherapeutic drugs. Plumbagin has been shown to act synergistically with various chemotherapeutic drugs and enhance their efficacy in drug-resistant cancers. The pleiotropic nature is believed to be due to plumbagin's unique structure, which contains a naphthoquinone ring and a hydroxyl group responsible for plumbagin's various biological responses. Despite limitations such as restricted bioavailability and delivery, recent developments aim to address these challenges and harness the potential of plumbagin as an anticancer therapeutics. This review delves into the structural aspect of the plumbagin molecule contributing to its pleiotropic nature, explores the diverse mechanism that it targets, and discusses emerging strategies to overcome its limitations.

Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Chemotaxonomy compared to morphological and anatomical taxonomy of five Hibiscus species.

Hibiscus is a charismatic genus of the Malvaceae family that is noted for its diversity, lacking identifiable characteristics for distinguishing its various species. Therefore, there is an urgent need to develop authentication methods for genus delimitation and species delineation. The present study aims to discern the taxonomic relationships between the well-known, globally familiar, and economically important five Hibiscus species, namely: H. × rosa-sinensis, H. sabdariffa, H. schizopetalus, H. syriacus and H. tiliaceus based on traditional morphological and anatomical characteristics compared to the contemporary chemotaxonomy. In this context, the leaf-based methanolic extracts of the studied species were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS) to estimate their secondary metabolites similarity. In addition, selected qualitative morphological and anatomical traits including leaf venation patterns, epidermal micromorphology, stomata types and trichomes diversity, petiole serial sectioning (outline, adaxial groove features, vasculature traces arrangement), and midrib characteristics of the studied species were investigated. The results of both chemotaxonomy and traditional taxonomy exhibited a remarkable agreement in the delineation of the five studied species. Specifically, the chemotaxonomy-based dendrogram separates the studied species into two main clusters with the H. sabdariffa as an outlier species in a single cluster and the remaining four species as another cluster with variant distances in its similarity indices. Similarly, the traditional morphological and anatomical characteristics revealed distinct traits for H. sabdariffa compared to the remaining four species. The findings of this study highlight the significance of integrating the structural features with phytochemicals profiling as a potential approach that could be harnessed for the delineation of the taxonomically challenging Hibiscus genus.

Exploring Bioactive Components and Assessing Antioxidant and Antibacterial Activities in Five Seaweed Extracts from the Northeastern Coast of Algeria.

The main goal of this study was to assess the bioactive and polysaccharide compositions, along with the antioxidant and antibacterial potentials, of five seaweeds collected from the northeastern coast of Algeria. Through Fourier transform infrared spectroscopy analysis and X-ray fluorescence spectroscopy, the study investigated the elemental composition of these seaweeds and their chemical structure. In addition, this study compared and identified the biochemical makeup of the collected seaweed by using cutting-edge methods like tandem mass spectrometry and ultra-high-performance liquid chromatography, and it searched for new sources of nutritionally valuable compounds. According to the study's findings, Sargassum muticum contains the highest levels of extractable bioactive compounds, showing a phenolic compound content of 235.67 ± 1.13 µg GAE·mg-1 and a total sugar content of 46.43 ± 0.12% DW. Both S. muticum and Dictyota dichotoma have high concentrations of good polyphenols, such as vanillin and chrysin. Another characteristic that sets brown algae apart is their composition. It showed that Cladophora laetevirens has an extracted bioactive compound content of 12.07% and a high capacity to scavenge ABTS+ radicals with a value of 78.65 ± 0.96 µg·mL-1, indicating high antioxidant activity. In terms of antibacterial activity, S. muticum seaweed showed excellent growth inhibition. In conclusion, all five species of seaweed under investigation exhibited unique strengths, highlighting the variety of advantageous characteristics of these seaweeds, especially S. muticum.