Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

Osteoarthritis (OA) is a common degenerative joint disease and is a leading cause of disability and reduced quality of life worldwide. There are currently no clinical treatments that can stop or slow down OA. Drugs have pain-relieving effects, but they do not slow down the course of OA and their long-term use can lead to serious side effects. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Autophagy is an intracellular protective mechanism, and targeting autophagy-related pathways has been found to prevent and treat various diseases. Attenuation of the autophagic pathway has now been found to disrupt cartilage homeostasis and plays an important role in the development of OA. Therefore, modulation of autophagic signaling pathways mediating cartilage homeostasis has been considered as a potential therapeutic option for OA. Phytochemicals are active ingredients from plants that have recently been found to reduce inflammatory factor levels in cartilage as well as attenuate chondrocyte apoptosis by modulating autophagy-related signaling pathways, which are not only widely available but also have the potential to alleviate the symptoms of OA. We reviewed preclinical studies and clinical studies of phytochemicals mediating autophagy to regulate cartilage homeostasis for the treatment of OA. The results suggest that phytochemicals derived from plant extracts can target relevant autophagic pathways as complementary and alternative agents for the treatment of OA if subjected to rigorous clinical trials and pharmacological tests.

Bioguided Isolation of Alkaloids and Pharmacological Effects of the Total Alkaloid Fraction from Aspidosperma pyrifolium Mart. (Apocynaceae)

Aspidosperma pyrifolium is used in traditional medicine to treat inflammatory disorders. The aim of the study was to perform phytochemical characterization and evaluate the anti-inflammatory, anti-nociceptive and acute toxicity effects of the total alkaloid fraction (TAF-Ap) from stem barks. Two monoterpenic indole alkaloids were isolated by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) and the structural elucidation was performed using 1D and 2D NMR analysis. As for toxicity, no animals died at 50 mg kg−1 and this concentration presented mild sedation and forced breathing within the first 24 h. The lethal dose capable of killing 50% of the animals (LD50) was estimated to be 160 mg kg−1. In the pharmacological tests, the models used were 1% carrageenan-induced paw edema and peritonitis, 1% formalin-induced nociception and 1% acetic acid-induced abdominal writhing in Swiss mice. The study made it possible to isolate 15-methoxyaspidospermine and 15-methoxypyrifolidine, corroborating the results of pharmacological assays, which showed anti-inflammatory and analgesic potential, especially at 30 mg kg−1 (p < 0.001). Thus, the species was shown to be a promising source of active substances, with special attention paid to its toxicological potential.

Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, cartilage damage and bone destruction. Although the pharmacological treatment of RA has evolved over the last few years, the new drugs have serious side effects and are very expensive. Thus, the research has been directed in recent years towards new possible targets. Among these targets, N-formyl peptide receptors (FPRs) are of particular interest. Recently, the mixed FPR1/FPR2 agonist Cpd43, the FPR2 agonist AT-01-KG, and the pyridine derivative AMC3 have been shown to be effective in RA animal models. As an extension of this research, we report here a new series of pyridinone derivatives containing the (substituted)phenyl acetamide chain, which was found to be essential for activity, but with different substitutions at position 5 of the scaffold. The biological results were also supported by molecular modeling studies and additional pharmacological tests on AMC3 have been performed in a rat model of RA, by repeating the treatments of the animals with 10 mg/kg/day of compound by 1 week.

Broad Efficacy of Scavenging Free Radicals: Cordyceps sp.

Scavenging free radical potency of cordycepin is the major bioactive segment extricated from Cordyceps species. In some new years, Cordyceps has gotten growing thought inferable from its distinctive restorative/pharmacological tests. This assessment reviews continuous explores on the counter oxidant impacts and the associated analyses of Cordyceps species. The results from our review show that Cordyceps of the cordycepin applies protective effects against hostile to oxidant injury for certain, afflictions including constant obstructive pneumonic infection (COPD), hepatitis, asthma, cerebral paralysis, Parkinson’s illness (PD), coronary course sickness (CAD), Alzheimer illness, respiratory failure, malignancy infection, maturing, waterfalls, and mind brokenness. Cordyceps coordinates the NF-κB, RIP2/Caspase-1, Akt/GSK-3β/p70S6K, TGF-β/Smads, and Nrf2/HO-1 hailing pathways among others of cordycepin. A couple of assessments focusing in on Cordyceps auxiliaries were surveyed and found to down metabolic speed of Cordyceps and augmentation its bioavailability. In addition, cordycepin further developed opposition, prevented the duplication of viral RNA, and covered cytokine storms, therefore proposing its capacity to treat COVID-19 and other viral defilements. From the accumulated and assessed information, this article gives the speculative reason to the clinical usages of cordycepin and inspects the way for future assessments focusing in on expanding the restorative use of Cordyceps species. Cordycepin and its analogs show unfathomable potential as the accompanying new class of against oxidant specialists.

Javanese Turmeric (Curcuma xanthorrhiza Roxb.): Ethnobotany, Phytochemistry, Biotechnology, and Pharmacological Activities

Curcuma xanthorrhiza Roxb., locally famed as Temulawak, has been extensively utilized in Indonesia as medicinal and nutritional plants since immemorial time. The rhizome of this plant is an important ingredient for jamu formulation (Indonesian traditional medicine). C. xanthorrhiza is traditionally used to treat several ailments such as lack of appetite, stomach disorder, liver illness, constipation, bloody diarrhea, dysentery, arthritis, children’s fevers, hypotriglyceridaemia, hemorrhoids, vaginal discharge, rheumatism, and skin eruptions. To date, over 40 active compounds, including terpenoids, curcuminoids, and other phenolic compounds, have been isolated and identified from C. xanthorrhiza Roxb. Some pharmacological tests reported that C. xanthorrhiza Roxb. has antioxidant, antimicrobial, anti-inflammatory, anticancer and antitumor, antidiabetic, and skincare and hepatoprotective properties. Efforts for biotechnologically production of C. xanthorrhiza have also been conducted, resulting in some micropropagation protocols of this plant. The current review focuses on the botanical description and distribution, ethnomedicinal uses, production and conservation status, phytochemical properties, and pharmacological activities of C. xanthorrhiza Roxb. to provide accurate and reliable data for future researches and commercialization purposes.

The translational roadmap of the gut models, focusing on gut-on-chip

It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut microbiota, immune and neuroendocrine systems. Here we present a roadmap of the current models to facilitate the choice in preclinical and translational research with a focus on gut-on-chip. These micro physiological systems (MPS) are microfluidic devices that recapitulate in vitro the physiology of the intestine. We reviewed the gut-on-chips that had been developed in academia and industries as single chip and that have three main purpose: replicate the intestinal physiology, the intestinal pathological features, and for pharmacological tests.

Determination of medium lethal dose (LD50) and acute toxicity of formulation Cytoreg®, an ionic mixture of strong and weak acids

A series of toxicological and pharmacological tests were started in the bioterium of the University of Los Andes, in order to evaluate a new formulation for therapeutic purposes. The present work reports the results found regarding the LD50 and the acute toxicity of this formulation produced by Cytorex of Venezuela, S.A. The new formulation supplied in liquid form, containing a variety of acid atoms whose conjugated bases have different electrical charges. It constitutes an ion transport complex of positively charged cations and negatively charged anions in high concentrations that help regulate mitochondrial and cellular metabolism and utilizes the inorganic fluoride ion (HF) as the main active compound, as referred to by the supplier. All the concentrations described in this work are referred to hydrofluoric acid (HF), which is the active compound of the formulation. Conventional pharmacological methods were used and it was found that the average lethal dose in rats resulted in 44.83 mg/Kg, and of 0.82ml/Kg. At the concentration of minimum dose of 0,49 mL/Kg of weight, the surviving animals did not present apparent macroscopic lesions at necropsy.

Obese Animals as Models for Numerous Diseases: Advantages and Applications

With the advances in obesity research, a variety of animal models have been developed to investigate obesity pathogenesis, development, therapies and complications. Such obese animals would not only allow us to explore obesity but would also represent models to study diseases and conditions that develop with obesity or where obesity represents a risk factor. Indeed, obese subjects, as well as animal models of obesity, develop pathologies such as cardiovascular diseases, diabetes, inflammation and metabolic disorders. Therefore, obese animals would represent models for numerous diseases. Although those diseases can be induced in animals by chemicals or drugs without obesity development, having them developed as consequences of obesity has numerous advantages. These advantages include mimicking natural pathogenesis processes, using diversity in obesity models (diet, animal species) to study the related variabilities and exploring disease intensity and reversibility depending on obesity development and treatments. Importantly, therapeutic implications and pharmacological tests represent key advantages too. On the other hand, obesity prevalence is continuously increasing, and, therefore, the likelihood of having a patient suffering simultaneously from obesity and a particular disease is increasing. Thus, studying diverse diseases in obese animals (either induced naturally or developed) would allow researchers to build a library of data related to the patterns or specificities of obese patients within the context of pathologies. This may lead to a new branch of medicine specifically dedicated to the diseases and care of obese patients, similar to geriatric medicine, which focuses on the elderly population.

A tale of ptosis, pharmacological tests, and Pancoast tumour

Horner syndrome (HS) classically presents with ipsilateral blepharoptosis, pupillary miosis, and facial anhidrosis and caused by a lesion along the oculosympathetic pathway from the hypothalamus to eye. The diagnosis of HS in a patient presenting with partial ptosis may be easily missed in the Asian patient. This is mainly due to the dark irides, making detection of anisocoria on direct visualization difficult. Index of suspicion must be high, especially in the absence of any extraocular motility or lid abnormalities. We present a case where a healthy asymptomatic patient presented with partial ptosis and diagnosis of HS was eventually confirmed through pharmacological tests. Non-targeted imaging with a simple chest X-ray revealed an apical lung lesion which eventually turned out to be malignant. Although it is a typical textbook description, this case highlights the importance of careful history and examination in an otherwise healthy patient presenting with mild ptosis.