{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:33:51Z","timestamp":1787567631397,"version":"build-2736575974"},"reference-count":50,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_dmdi-2025-0096_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Endoplasmic reticular (ER) stress plays an important role in gene modulation and the consequent release of several inflammatory mediators i.e.,\u00a0cytokines and proteases, key players associated with systemic-induced inflammation in various liver diseases. Natural products containing bioactive compounds have emerged as better therapeutic agents, attributed to their affordability as well as inherent biological properties.\n                      <jats:italic>Withania somnifera<\/jats:italic>\n                      (WS, Ashwagandha) is recognized for its immunomodulatory activities in Ayurveda.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmdi-2025-0096_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The present study investigated the effects of WS in uninduced and tunicamycin (Tm)-stimulated inflammation as well as ER stress response in HepG2 cells. The cells were optimized for Tm stress induction time, concentration as well as treatment mode (pre-, co- or post-).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmdi-2025-0096_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was a substantial increase in ER stress and inflammation response after 24\u202fh at 40\u202f\u03bcg\/mL in the pretreatment group. WS treatment significantly inhibited ER stress response and inflammation in uninduced and Tm-induced stress groups in a dose-dependent approach. The activation of PERK\/eIF2\u03b1\/ATF4 and IRE1\u03b1\/JNK signaling cascades was inhibited by WS in both uninduced and Tm-stimulated cells. The molecular pathways involved in suppression of hepatic inflammation included NF-\u03baB, P38 and MAPK JNK which showed inhibition by WS. Suppression of inflammatory cytokine production\n                      <jats:italic>viz<\/jats:italic>\n                      . IL-1\u03b2, IL-6, and IL-18 was observed in both uninduced and stress-induced\u00a0cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmdi-2025-0096_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study suggests that WS is a potential candidate to prevent inflammation and ER stress response against ER-stress triggered inflammation in HepG2 ER\u00a0cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/dmpt-2025-0096","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:13:06Z","timestamp":1787562786000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Withania somnifera<\/i>\n                    ameliorates endoplasmic reticulum stress in human hepatocellular carcinoma HepG2 cells"],"prefix":"10.1515","author":[{"given":"Eshita","family":"Sharma","sequence":"first","affiliation":[{"name":"Phytoveda Pvt. Ltd. , Mumbai , India"},{"name":"Viridis Biopharma Pvt. Ltd. , Mumbai , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip","family":"Mehta","sequence":"additional","affiliation":[{"name":"Phytoveda Pvt. Ltd. , Mumbai , India"},{"name":"Viridis Biopharma Pvt. Ltd. , Mumbai , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4479-328X","authenticated-orcid":false,"given":"Anand","family":"Bhaskar","sequence":"additional","affiliation":[{"name":"Phytoveda Pvt. Ltd. , Mumbai , India"},{"name":"Viridis Biopharma Pvt. 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