Abdullah Al Mamun Sohag

Kynurenine pathway (KP) metabolite imbalance is implicated in perinatal brain injury, and KP metabolites are measured in human plasma and cerebrospinal fluid as markers of neuroinflammation. Methods validated in neonatal brain tissue or glial culture supernatant to the same standard are scarce, limiting comparisons across preclinical and clinical measurements. We optimised LC-MS/MS detection of tryptophan (TRYP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), quinolinic acid (QA), anthranilic acid and picolinic acid after protein precipitation and Enhanced Matrix Removal-Lipid clean-up, validated it against Clinical and Laboratory Standards Institute (CLSI) acceptance criteria in brain tissue homogenate and cell culture supernatant, and applied it to a rat model of neonatal stroke and immune-activated BV2 microglia, reporting KYN/TRYP, KYNA/KYN, 3-HK/3-HAA and QA/KYNA ratios. The lower limit of quantification was 6.53-34.17 nM; imprecision was 0.57-11.47%, accuracy was 84.9-108.3%, recovery was 83.2-112.3%, and matrix effect was 87.8-108.8%, with linear calibration (R ² > 0.99) over 6.5-2000 nM. KYN/TRYP and QA/KYNA ratios were higher in the stroke hemisphere than in control brain at 1, 7 and 14 days (p<0.001), and KYNA/KYN was lower; lipopolysaccharide- and cytokine-stimulated BV2 microglia showed the same change in all four ratios (p<0.01). The assay quantifies eight KP metabolites and four pathway-balance ratios in brain tissue and microglial supernatant within clinical acceptance limits, allowing direct comparison with KP ratios reported in human plasma and cerebrospinal fluid. Changes in these ratios after neonatal stroke identify KYN/TRYP and QA/KYNA as candidate targets for neonatal biofluid studies.

In this study, canola (Brassica napus L.) seedlings were treated with individual and combined salinity and lithium (Li) stress, with and without acetic acid (AA) or nitric acid (NO), to investigate their possible roles against these stresses. Salinity intensified Li-induced damage, and the principal component analysis revealed that this was primarily driven by increased oxidative stress, deregulation of sodium and potassium accumulation, and an imbalance in tissue water content. However, pretreatment with AA and NO prompted growth, re-established sodium and potassium homeostasis, and enhanced the defense system against oxidative and nitrosative damage by triggering the antioxidant capacity. Combined stress negatively impacted phenylalanine ammonia lyase activity, affecting flavonoids, carotenoids, and anthocyanin levels, which were then restored in canola plants primed with AA and NO. Additionally, AA and NO helped to maintain osmotic balance by increasing trehalose and proline levels and upregulating signaling molecules such as hydrogen sulfide, γ-aminobutyric acid, and salicylic acid. Both AA and NO improved Li detoxification by increasing phytochelatins and metallothioneins, and reducing glutathione contents. Comparatively, AA exerted more effective protection against the detrimental effects of combined stress than NO. Our findings offer novel perspectives on the impacts of combining salt and Li stress.

Fucoxanthin, belonging to the xanthophyll class of carotenoids, is a natural antioxidant pigment of marine algae, including brown macroalgae and diatoms. It represents 10% of the total carotenoids in nature. The plethora of scientific evidence supports the potential benefits of nutraceutical and pharmaceutical uses of fucoxanthin for boosting human health and disease management. Due to its unique chemical structure and action as a single compound with multi-targets of health effects, it has attracted mounting attention from the scientific community, resulting in an escalated number of scientific publications from January 2017 to February 2022. Fucoxanthin has remained the most popular option for anti-cancer and anti-tumor activity, followed by protection against inflammatory, oxidative stress-related, nervous system, obesity, hepatic, diabetic, kidney, cardiac, skin, respiratory and microbial diseases, in a variety of model systems. Despite much pharmacological evidence from in vitro and in vivo findings, fucoxanthin in clinical research is still not satisfactory, because only one clinical study on obesity management was reported in the last five years. Additionally, pharmacokinetics, safety, toxicity, functional stability, and clinical perspective of fucoxanthin are substantially addressed. Nevertheless, fucoxanthin and its derivatives are shown to be safe, non-toxic, and readily available upon administration. This review will provide pharmacological insights into fucoxanthin, underlying the diverse molecular mechanisms of health benefits. However, it requires more activity-oriented translational research in humans before it can be used as a multi-target drug.

Coronavirus disease-19 (COVID-19) pandemic is a global threat caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The viral infection dysregulates the functions of the renin-angiotensin system (RAS) through an interaction between SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2), leading to an upregulated level of Angiotensin II (Ang II) in blood plasma. The enhanced level of Ang II may contribute to various pathophysiological events, including vasoconstriction, oxidative stress, endothelial dysfunction, inflammation, beta-cell dysfunction, and many others. These phenomena are associated with developing multiple chronic diseases, including hypertension, cardiovascular disease, diabetes, lung disease, renal disease, and many other comorbidities in COVID-19 patients. Thus, the SARS-CoV-2 infection may contribute to severe conditions and higher mortality in COVID-19 patients with underlying comorbidities. Several synthetic drugs, especially RAS blockades, are currently prescribed to COVID-19 patients to minimize the severity of these comorbidities by limiting the deleterious effects of Ang II. However, these chemosynthetic drugs are limited by several side effects such as persistent cough, fetal abnormalities, hepatic disorder as well as promotion in the occurrence of new chronic diseases. These drawbacks raise an investigation to explore comparatively safe alternatives for COVID-19 patients. From this point of view, we have anticipated that applications of multifunctional food-derived bioactive peptides could be a promising approach through their preventive and therapeutic actions against underlying chronic complications in COVID-19 patients. This review enlightened the disease preventive and immunomodulatory effects of food-derived bioactive peptides that may enhance the survivability and vitality of COVID-19 patients with chronic complications.

Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb–drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.

Bioactive plant derived compounds are important for a wide range of therapeutic applications, and some display promising anticancer properties. Further evidence suggests that phytochemicals modulate autophagy and apoptosis, the two crucial cellular pathways involved in the underlying pathobiology of cancer development and regulation. Pharmacological targeting of autophagy and apoptosis signaling using phytochemicals therefore offers a promising strategy that is complementary to conventional cancer chemotherapy. In this review, we sought to highlight the molecular basis of the autophagic-apoptotic pathway to understand its implication in the pathobiology of cancer, and explore this fundamental cellular process as a druggable anticancer target. We also aimed to present recent advances and address the limitations faced in the therapeutic development of phytochemical-based anticancer drugs.

Alzheimer’s disease (AD) is a degenerative brain disorder characterized by a progressive decline in memory and cognition, mostly affecting the elderly. Numerous functional bioactives have been reported in marine organisms, and anti-Alzheimer’s agents derived from marine resources have gained attention as a promising approach to treat AD pathogenesis. Marine sterols have been investigated for several health benefits, including anti-cancer, anti-obesity, anti-diabetes, anti-aging, and anti-Alzheimer’s activities, owing to their anti-inflammatory and antioxidant properties. Marine sterols interact with various proteins and enzymes participating via diverse cellular systems such as apoptosis, the antioxidant defense system, immune response, and cholesterol homeostasis. Here, we briefly overview the potential of marine sterols against the pathology of AD and provide an insight into their pharmacological mechanisms. We also highlight technological advances that may lead to the potential application of marine sterols in the prevention and therapy of AD.

Macroalgae are gaining popularity as unconventional food sources because of their essential nutrients and bioactive metabolites. Nutrient composition, phytochemical profile, and antioxidant property of five macroalgae have been investigated. The proximate composition analysis revealed the highest protein (19.99%) and fiber (26.82%) in Gracilaria tenuistipitata, crude fat (3.85%) in Spatoglossum asperum, and ash (14.71%) in Hypnea boergesenii. Mineral analysis indicated substantially high calcium and sodium in H. boergesenii (756.924 and 17.62 mg % DM, respectively), potassium in S. tenerrimum (523.77 mg% DM), iron in Enteromorpha intestinalis (98.27 mg% DM), copper in S. tenerrimum (2.24 mg% DM), and zinc in S. asperum (1.90 mg% DM). Chlorophyll and carotenoid were highest in E. intestinalis (1.57 mg/g) and S. asperum (0.19 mg/g), respectively. Phytochemical screening confirmed the presence of tannins, saponins, alkaloids, and flavonoids in algae. Agar extraction with 6% NaOH resulted in maximum agar yield from G. tenuistipitata. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay indicates that H. boergesenii exhibited a moderate antioxidant activity (IC₅₀ value, 91.06 ± 6.44 μg/mL). Together, these findings indicate that marine algae could be a rich source of essential nutrients and bioactive compounds with pharmacological potential suggesting their use as promising functional food ingredients for human well-being.