Citicoline and COVID-19-Related Cognitive and Other Neurologic Complications

With growing concerns about COVID-19’s hyperinflammatory condition and its potentially damaging impact on the neurovascular system, there is a need to consider potential treatment options for managing short- and long-term effects on neurological complications, especially cognitive function. While maintaining adequate structure and function of phospholipid in brain cells, citicoline, identical to the natural metabolite phospholipid phosphatidylcholine precursor, can contribute to a variety of neurological diseases and hypothetically toward post-COVID-19 cognitive effects. In this review, we comprehensively describe in detail the potential citicoline mechanisms as adjunctive therapy and prevention of COVID-19-related cognitive decline and other neurologic complications through citicoline properties of anti-inflammation, anti-viral, neuroprotection, neurorestorative, and acetylcholine neurotransmitter synthesis, and provide a recommendation for future clinical trials.

Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming

Lactic acidosis, the extracellular accumulation of lactate and protons, is a consequence of increased glycolysis triggered by insufficient oxygen supply to tissues. Macrophages are able to differentiate from monocytes under such acidotic conditions, and remain active in order to resolve the underlying injury. Here we show that, in lactic acidosis, human monocytes differentiating into macrophages are characterized by depolarized mitochondria, transient reduction of mitochondrial mass due to mitophagy, and a significant decrease in nutrient absorption. These metabolic changes, resembling pseudostarvation, result from the low extracellular pH rather than from the lactosis component, and render these cells dependent on autophagy for survival. Meanwhile, acetoacetate, a natural metabolite produced by the liver, is utilized by monocytes/macrophages as an alternative fuel to mitigate lactic acidosis-induced pseudostarvation, as evidenced by retained mitochondrial integrity and function, retained nutrient uptake, and survival without the need of autophagy. Our results thus show that acetoacetate may increase tissue tolerance to sustained lactic acidosis.

Pemberdayaan Masyarakat dalam Pembuatan Lulur Tradisional dari Beras dan Kunyit di Kecamatan Cempaka Banjarbaru

As we get older, the skin will undergo an aging process. Aging is caused by a variety of factors both from within and from outside the body. As a traditional raw material, turmeric (Curcuma longa L) contains natural metabolite compounds in the form of curcumin. Rice and turmeric are ingredients often found in the community. The use of rice for beauty is still very little known to the public. The target of this activity is the community of Cempaka Banjarbaru, South Kalimantan. The objective of this activity is to improve the community's skills in making traditional scrubs. The method is to provide training/demonstrations in making scrub preparations. The result of this community service activity is that people can practice making scrubs from turmeric and rice. This activity concludes that the scrub products processed by the community service team can be well received by the residents, which is indicated by the enthusiasm of the residents asking questions and trying the scrub products made.

Enhancement of Anticancer Potential of Pterostilbene Derivative by Chalcone Hybridization

Pterostilbene, a natural metabolite of resveratrol, has been indicated as a potent anticancer molecule. Recently, several pterostilbene derivatives have been reported to exhibit better anticancer activities than that of the parent pterostilbene molecule. In the present study, a series of pterostilbene derivatives were designed and synthesized by the hybridization of pterostilbene, chalcone, and cinnamic acid. The cytotoxic effect of these hybrid molecules was determined using two oral cancer cell lines, HSC-3 and OECM-1. (E)-3-(2-((E)-4-Hydroxystyryl)-4,6-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (4d), with IC50 of 16.38 and 18.06 μM against OECM-1 and HSC-3, respectively, was selected for further anticancer mechanism studies. Results indicated that compound 4d effectively inhibited cell proliferation and induced G2/M cell cycle arrest via modulating p21, cyclin B1, and cyclin A2. Compound 4d ultimately induced cell apoptosis by reducing the expression of Bcl-2 and surviving. In addition, cleavage of PARP and caspase-3 were enhanced following the treatment of compound 4d with increased dose. To conclude, a number of pterostilbene derivatives were discovered to possess potent anticancer potentials. Among them, compound 4d was the most active, more active than the parent pterostilbene.

Effect of Polyploidy Induction on Natural Metabolite Production in Medicinal Plants

Polyploidy plays an important role in plant diversification and speciation. The ploidy level of plants is associated with morphological and biochemical characteristics, and its modification has been used as a strategy to alter the quantitative and qualitative patterns of secondary metabolite production in different medicinal plants. Polyploidization can be induced by many anti-mitotic agents, among which colchicine, oryzalin, and trifluralin are the most common. Other variables involved in the induction process include the culture media, explant types, and exposure times. Due to the effects of polyploidization on plant growth and development, chromosome doubling has been applied in plant breeding to increase the levels of target compounds and improve morphological characteristics. Prompted by the importance of herbal medicines and the increasing demand for drugs based on plant secondary metabolites, this review presents an overview of how polyploidy can be used to enhance metabolite production in medicinal plants.

Comparative Stability of Two Anti-Hyperpigmentation Agents: Kojic Acid as a Natural Metabolite and Its Di-Palmitate Ester, Under Oxidative Stress; Application to Pharmaceutical Formulation Design

Purpose: Kojic acid a natural metabolite (KA) and its dipalmitate ester, kojic acid dipalmitate (Kadp) are both prescribed to treat skin hyperpigmentation. Stress test reveals the intrinsic stability of active ingredients and leads to selection of the suitable formulations. This research evaluates the comparative stability of KA and its di-palmitate ester under liquid oxidative stress. Methods: The HPLC-UV/PDA method with a C18 column was utilized. Liquid oxidative stress was induced using hydrogen peroxide (H2O2). Degradation was separately induced for each drug, and they were compared to each other. Results: Kadp degraded more rapidly in similar liquid oxidative stress conditions than KA did. The superior degradation model was the first order for both drugs based on the MPE values, indicating the dependency of the reaction rate on the initial concentration of the reactive substance. Ring opening was proposed as the most possible theory for KA and Kadp oxidative degradation. Conclusion: It is suggested to use KA instead of Kadp in less stable formulations, such as extemporaneous preparations. The incorporation of antioxidant excipients in Kadp formulations is recommended for yielding better stability results. Formulating Kadp in the internal phase of o/w emulsion formulations may protect this susceptive molecule from oxidative degradation during the shelf life of the pharmaceutical preparation. Further studies are required to study the exact mechanism of the degradation process.

Synthesis of New Functionally Substituted 9-Azabicyclo[4.2.1]nona-2,4,7-Trienes by Cobalt(I)-Catalyzed [6π + 2π]-Cycloaddition of N-Carbocholesteroxyazepine to Alkynes

Catalytic [6π + 2π]-cycloaddition of N-carbocholesteroxyazepine with functionally substituted terminal alkynes and 1,4-butynediol was performed for the first time under the action of the Co(acac)2(dppe)/Zn/ZnI2 three-component catalytic system. The reaction gave previously undescribed but promising 9-azabicyclo[4.2.1]nona-2,4,7-trienes (in 79–95% yields), covalently bound to a natural metabolite, cholesterol. The structure of the synthesized azabicycles was confirmed by analysis of one- and two-dimensional (1H, 13C, DEPT 13C, COSY, NOESY, HSQC, HMBC) NMR spectra.

Succinic acid derivatives: influence on the metabolic factors of the development of fatigue and working capacity under physical loads

A study has been carried out on the effect of the domestic pharmacological armadin long preparation (2-ethyl-6-methyl-3-hydroxypyridine succinate) on the physical working capacity of athletes under the maximum in-tensity force loads characteristic of modern sports. Since pharmacology in sports is constantly searching for non-toxic drugs of the metabolithotropic origin that would have the ability to promote physical efficiency and slow down fatigue without toxic effects on the body, we have chosen for our research a drug based on succinic acid, which is a natural metabolite of the Krebs cycle. It has been shown that the armadin long preparation, when applied on a course for three weeks, positively affects the parameters of special working capacity associated with the improvement of the oxygen-transport function of blood. The metabolic basis of this phenomenon is the inhibition of a decrease in the pH of the internal environment of the body with the subsequent development of lactate-acidosis and the ability of the armadin long drug to accelerate the processes of angiogenesis, and, accordingly, the transport of oxygen to the athlete’s working muscles. The intensity of the formation of new growth factor (VEGF). Such data substantiate the expediency of the use of succinic acid-based agents to prevent negative metabolic changes and to slow down the onset of fatigue in athletes under intense physical loads

Microbial Pyrrolnitrin: Natural Metabolite with Immense Practical Utility

Pyrrolnitrin (PRN) is a microbial pyrrole halometabolite of immense antimicrobial significance for agricultural, pharmaceutical and industrial implications. The compound and its derivatives have been isolated from rhizospheric fluorescent or non-fluorescent pseudomonads, Serratia and Burkholderia. They are known to confer biological control against a wide range of phytopathogenic fungi, and thus offer strong plant protection prospects against soil and seed-borne phytopathogenic diseases. Although chemical synthesis of PRN has been obtained using different steps, microbial production is still the most useful option for producing this metabolite. In many of the plant-associated isolates of Serratia and Burkholderia, production of PRN is dependent on the quorum-sensing regulation that usually involves N-acylhomoserine lactone (AHL) autoinducer signals. When applied on the organisms as antimicrobial agent, the molecule impedes synthesis of key biomolecules (DNA, RNA and protein), uncouples with oxidative phosphorylation, inhibits mitotic division and hampers several biological mechanisms. With its potential broad-spectrum activities, low phototoxicity, non-toxic nature and specificity for impacts on non-target organisms, the metabolite has emerged as a lead molecule of industrial importance, which has led to developing cost-effective methods for the biosynthesis of PRN using microbial fermentation. Quantum of work narrating focused research efforts in the emergence of this potential microbial metabolite is summarized here to present a consolidated, sequential and updated insight into the chemistry, biology and applicability of this natural molecule.