A patent review on HMGB1 inhibitors for the treatment of liver diseases.

INTRODUCTION: HMGB1 is a non-histone chromatin protein released or secreted in response to tissue damage or infection. Extracellular HMGB1, as a crucial immunomodulatory factor, binds with several different receptors to innate inflammatory responses that aggravate acute and chronic liver diseases. The increased levels of HMGB1 have been reported in various liver diseases, highlighting that it represents a potential biomarker and druggable target for therapeutic development. AREAS COVERED: This review summarizes the current knowledge on the structure, function, and interacting receptors of HMGB1 and its significance in multiple liver diseases. The latest patented and preclinical studies of HMGB1 inhibitors (antibodies, peptides, and small molecules) for liver diseases are summarized by using the keywords 'HMGB1,' 'HMGB1 antagonist, HMGB1-inhibitor,' 'liver disease' in Web of Science, Google Scholar, Google Patents, and PubMed databases in the year from 2017 to 2023. EXPERT OPINIONS: In recent years, extensive research on HMGB1-dependent inflammatory signaling has discovered potent inhibitors of HMGB1 to reduce the severity of liver injury. Despite significant progress in the development of HMGB1 antagonists, few of them are approved for clinical treatment of liver-related diseases. Developing safe and effective specific inhibitors for different HMGB1 isoforms and their interaction with receptors is the focus of future research.

Isolation and microbial transformation of tea sapogenin from seed pomace of Camellia oleifera with anti-inflammatory effects.

In the current study, tea saponin, identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel., was meticulously extracted and hydrolyzed to yield five known sapogenins: 16-O-tiglogycamelliagnin B (a), camelliagnin A (b), 16-O-angeloybarringtogenol C (c), theasapogenol E (d), theasapogenol F (e). Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites (a1-a6). The anti-inflammatory potential of these compounds was assessed using pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns molecules (DAMPs)-mediated cellular inflammation models. Notably, compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1)-induced inflammation, surpassing the efficacy of the standard anti-inflammatory agent, carbenoxolone. Conversely, compounds d, a3, and a6 selectivity targeted endogenous HMGB1-induced inflammation, showcasing a pronounced specificity. These results underscore the therapeutic promise of C. oleifera seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.

Impact of psychiatric comorbidity on quality of life and activities of daily living among patients suffering from chronic kidney disease undergoing hemodialysis.

Introduction: Chronic Kidney Disease (CKD) is a debilitating illness that impairs an individual's physical and social functioning and ultimately affects the quality of life (QOL). Aim: To determine the impact of psychiatric comorbidity on QOL and activities of daily living in individuals suffering from CKD undergoing hemodialysis. Materials and Methods: Fifty subjects suffering from CKD undergoing hemodialysis were consequently enrolled in the department of medicine. Institutional ethics committee permission was obtained before the start of the study. The interview was conducted only after the hemodialysis procedure. Consent was obtained and socio-demographic details were noted in the socio-demographic proforma. Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to assess psychiatric comorbidity. QOL was assessed on Short Form-36 (SF-36). Katz Index of Independence of Activities of Daily Living scale (KADL) was used to assess the activities of living of such individuals. Results: 46% (n = 23) of subjects suffering from CKD had psychiatric co-morbidity. The most common psychiatric disorder observed was moderate depressive disorder (14%, n = 7) followed by adjustment disorder (12%, n = 6). QOL on SF-36 in all eight domains was low compared to the general population. There was a high statistically significant negative impact of psychiatric comorbidity on QOL on eight domains of SF-36 and activities of daily living. (P = 0.001). Conclusion: Psychiatric co-morbidity is common in CKD patients on hemodialysis. Quality of life is lower compared to the general population. There is a negative impact of psychiatric co-morbidity on quality of life and activities of daily living.

Psychiatric morbidity among patients suffering from Vitiligo.

Background: Vitiligo is a chronic acquired, stigmatizing disease characterized by discoloration of skin and mucous membranes. Patients suffering from this condition suffer from a lack of confidence and psychological stress. Aim: To assess depression, anxiety, and social anxiety among patients suffering from vitiligo. Material and Method: This hospital-based cross-sectional, observational, descriptive study was carried out in a tertiary care center on 100 patients suffering from vitiligo, who were consecutively enrolled after informed consent from the outpatient department (OPD) of the dermatology department. Permission was obtained from the institutional ethics committee Diagnosis of vitiligo was made by two consultants from the department of dermatology. Sociodemographic variables were recorded in the sociodemographic form. The General Health Questionnaire-12 (GHQ-12) was applied to all 100 patients. Patients who scored >3 on GHQ-12 were further subjected to the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Social Interaction Anxiety Scale. Results were statistically analyzed on SPSS-22.0 (IBM, Armonk, USA). Results: Of all the patients, 55% (n = 55) had a GHQ score >3 (i.e., Psychiatric morbidity was present in 55% of patients.). Out of 50 patients in the age group of 18-25 years, 41 patients in the age groups of 26-35 years, and 9 patients in the age groups of 36-45 years, 22 (44%), 17 (42.1%), and 6 patients had psychiatric morbidity, respectively. Of the total number of patients, 46% had depression according to the HAM-D scale. Of all the patients, 18% had mild, 22% had moderate, and 6% had severe depression. Age-wise analysis showed that out of 50 patients in the age group of 18-25 years, 41 patients in the age group of 26-35 years, and 9 patients in the age group of 36-45 years, 22 (44%), 20 (48.7%), and 4 patients had depression, respectively. Of the patients who had depression, 39% were male and 58% were female. On HAM-A, 47% of the patients had anxiety; 33% had mild, 12% had moderate, and 2% had severe anxiety. Age-wise analysis showed that out of 50 patients in the age group of 18-25, 41 patients in the age group of 26-35 years, and 9 patients in the age group of 36-45 years, 20 (40%), 23 (56.1%), and 3 patients had anxiety, respectively. On SIAS, 36% of the patients had social anxiety. Out of 50 patients in the age group of 18-25 years, 41 patients in the age group of 26-35 years, and 9 patients in the age group of 36-45 years, 23 (46%), 9 (7.8%) and 4 patients had social anxiety, respectively. According to gender-wise distribution, 17% of male and 63% of female patients had social anxiety. Conclusion: A high prevalence of anxiety, depression, and social anxiety has been observed in this present study. Therefore, importance should be given to psychiatric evaluation of such patients and, if required, necessary interventions should be undertaken to improve their quality of life.

Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages.

For the discovery of new pentacyclic triterpenes as a potential anti-inflammatory agent, microbial transformation of uvaol by Penicilium griseofulvum CICC 40293 and Streptomyces griseus ATCC 13273 was investigated. Stereoselective hydroxylation and epoxidation reactions were observed in the biotransformation. Moreover, six new metabolites were isolated and structurally elucidated by HR-ESI-MS and NMR spectrum. All the compounds were evaluated upon the inhibitory effects of nitric oxide (NO) release in RAW 264.7 cells induced by lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1). Among them, compound 3 (13, 28-epoxy-3ß, 7ß, 21ß-trihydroxy-urs-11-ene) with the unique epoxy structure and compound 5 (3ß, 21ß, 24, 28-tetrahydroxy-urs-12-en-30-oic acid), exhibited a considerable inhibitory effect on both models while compound 2 (urs-12-ene-3ß, 7ß, 21ß, 28-tetraol) showed a significant bias in the LPS-induced inflammatory response with IC50 value of 2.22 µM. Therefore, this study could provide some insights on the discovery of the pentacyclic triterpene leads for the treatment of either DAMPs or PAMPs triggered inflammation.

Microbial transformation of pentacyclic triterpenes for anti-inflammatory agents on the HMGB1 stimulated RAW 264.7 cells by Streptomyces olivaceus CICC 23628.

High mobility group box-1 protein (HMGB1) is a typical Damage-Associated Molecular Patterns (DAMPs) released in response to cellular inflammation. The pentacyclic triterpenes (PTs) are considered to be the natural inhibitors against HMGB1-related inflammation. To explore new lead compounds of PTs as anti-inflammatory agents, biotransformation of four PTs by Streptomyces olivaceus CICC 23628 was investigated in this study. As a result, thirteen unique 3,4-seco-triterpenes metabolites were isolated and twelve of them were first identified and reported. Structures of metabolites were determined based on HR-ESI-MS, 1D/2D NMR, and single-crystal X-ray diffraction. Furthermore, all compounds were subjected to the bioassay on the model of HMGB1-stimulated RAW 264.7 cells to evaluate their anti-inflammatory activity through nitric oxide (NO) inhibition activity. Compounds 3b (3,4-seco-olean-12-en-4,21α,22ß,24-tetrahydroxy-ol-3-oic acid) and 2b (3,4-seco-olean-12-en-4,21ß,22ß,24,29-pentahydroxy-ol-3-oic acid) exhibited NO inhibitory activity with IC50 values of 15.94 µM and 36.00 µM, respectively. Thus, indicating their potential as HMGB1 inhibitors and in developing potent anti-inflammatory agents. This work provides an operationally simple, efficient method for the rapid diversification of the PTs scaffold for a variety of distinctive 3,4-seco-triterpenes to facilitate the discovery of potential anti-inflammatory compounds.

Derivatization of Soyasapogenol A through Microbial Transformation for Potential Anti-inflammatory Food Supplements.

For the optimum use of soyasaponins isolated from soybean cake and to explore the potential anti-inflammatory agents from pentacyclic triterpenes as natural food supplements, microbial transformation of soyasapogenol A was carried out. Four strains of microbes, including Bacillus megaterium CGMCC 1.1741, Penicillium griseofulvum CICC 40293, Bacillus subtilis ATCC 6633, and Streptomyces griseus ATCC 13273, showed robust catalytic capacity to the substrate. Preparative biotransformation and column chromatographic purification led to the isolation of 10 novel and 1 reported metabolites. The structure elucidation was performed using 1D/2D NMR and HR-ESI-MS analytical method. Several novel tailoring reactions, such as allyl oxidation, C-C double bond rearrangement, hydroxylation, dehydrogenation, and glycosylation, were observed in the biotransformation. In the follow-up bioassay, most of the metabolites exhibited low cytotoxicity and potent inhibitory activity against the production of nitric oxide (NO) in RAW 264.7 cells stimulated by lipopolysaccharide. Especially compound 6 (3-oxo-11α,21ß,22ß,24-tetrahydroxy-olean-12-ene) showed comparable activity to the positive control of quercetin with an IC50 value of 16.70 µM. These findings provided an experimental approach to achieve the derivatization of natural aglycons in soybeans through microbial transformation for developing potent anti-inflammatory food supplements.