In a rat model of ventilator-induced lung injury (VILI), SSD reduced pulmonary neutrophil infiltration, myeloperoxidase levels and pro-inflammatory cytokines (MIP-2, IL-6 and TNF-α), while elevating anti-inflammatory mediators (TGF-β1 and IL-10) (21). SSD also reduced OS and apoptosis in lung tissue by downregulating caspases-3 and pro-apoptotic protein Bax, while upregulating the anti-apoptotic protein Bcl-2. These effects suggest that SSD may alleviate VILI by suppressing inflammation, OS and apoptosis (21). Another study demonstrated that SSD reduced LPS-induced inflammation and apoptosis in MLE-12 lung epithelial cells and, in vivo, decreased pathological damage, inflammation and apoptosis in cecum ligation and perforation-induced mouse septic acute lung injury model (55).

Idiopathic pulmonary fibrosis, a group of heterogeneous parenchymal lung disorders characterized by chronic progressive fibrosis, represents one of the most severe interstitial lung diseases (56). Sun et al (44) reported that SSD inhibits human embryonic lung fibroblast proliferation and collagen production [Collagen-1 (Col-1), α-smooth muscle actin (α-SMA)] via modulation of the TGF-β1/Smads pathway, exerting an antifibrotic effect. A recent study revealed that SSD reduces the expression of angiotensin-1 (Ang-1), Ang-2 and Tie-2 (tyrosine kinase receptors with immunoglobulin and epidermal growth factor homology domains-2) in the angiopoietin/Tie2 pathway, which may help alleviate pulmonary inflammation in bleomycin-induced mice (administered via intratracheal injection) by inhibiting angiogenesis and fibrosis (57).

Excessive acetaminophen (APAP) intake can lead to acute liver injury, which can be fatal and necessitates effective pharmacological intervention (58). Liu et al (59) found that SSD protected mice from APAP-induced hepatotoxicity by primarily inhibiting NF-κB and STAT3-mediated inflammatory signaling pathways (IL-6, C-C motif chemokine ligand 2, IL-10). Another study indicated that SSD mitigated carbon tetrachloride-induced acute hepatocyte damage by suppressing OS and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in HL-7702 cells (60). Similar protective effects were observed in animal models (61), where SSD administration led to reduced MDA and superoxide production in carbon tetrachloride-treated mouse liver tissue while enhancing SOD, glutathione peroxidase (GPx) and catalase activities. In addition, protein levels of caspase 1, NLRP3, apoptosis-associated speck-like protein, IL-1β and IL-18 were diminished (61), supporting conclusions drawn from in vitro experiments.

ALD, encompassing a range of liver damage due to chronic excessive alcohol intake, has become a significant global health concern (62). Hepatic stellate cells (HSCs) play a pivotal role in ALD progression, with activated HSCs acting as a primary source of extracellular matrix (ECM) in the liver (63). Jiang et al (64) demonstrated that SSD suppressed proliferation and promoted apoptosis in acetaldehyde-activated rat HSC-T6 cells by stimulating autophagosome formation. SSD treatment increased caspase-3 and Bax expression while reducing Ki67 and Bcl-2 levels. Despite its therapeutic potential, SSD has poor bioavailability, stability and solubility, which limits its clinical application. A promising study aimed to enhance SSD's efficacy by formulating SSD-loaded liposomes using a thin-film hydration method (65). Compared to the group treated with SSD alone, mice administered SSD liposomes showed significantly lower serum alanine aminotransferase, aspartate aminotransferase, MDA, TNF-α, total cholesterol and triglyceride levels in liver homogenates, while GPx and total SOD levels were significantly elevated. These observations suggest that SSD liposomes exhibit enhanced hepatoprotective effects in alleviating alcoholic hepatitis in mice, likely due to their improved antioxidative and anti-inflammatory properties (65).

Adipogenesis is the developmental process by which preadipocytes differentiate into mature adipocytes, leading to fat accumulation (66). Research has shown that SSD suppresses adipogenesis in 3T3-L1 adipocytes by promoting AMP-activated protein kinase phosphorylation and its substrate acetyl-CoA carboxylase during the early stage of adipogenesis, while concurrently inhibiting the phosphorylation of the ERK1/2 and p38 MAPK pathways (67). In a study focused on SSD's effects on NAFLD, SSD was found to significantly reduce fatty acid biosynthesis by downregulating fatty acid synthase (FASN) and acetyl-CoA carboxylases α (ACACA) expression and to enhance fatty acid degradation through increased expression of COX1 and carnitine palmitoyltransferase-1α (CPT1α) (22). Building on these outcomes, Gu et al (68) conducted further investigations using a high-fat diet (HFD)- and fructose water-induced metabolic dysfunction-associated fatty liver disease mouse model along with HepG2 cells, primary mouse hepatocytes and adipocytes. They discovered that SSD acts as a potent peroxisome proliferator-activated receptor α (PPARα) activator, promoting fatty acid oxidation in hepatocytes and adipocytes while upregulating insulin-induced genes 1 and 2 (INSIG1/2) expression, which inhibits sterol regulatory element-binding protein 1c (SREBP-lc) maturation and thereby reduces fatty acid production. Of note, the lipid-regulating effects of SSD were nullified by the PPARα inhibitor GW6471, indicating that SSD mitigates metabolism-related fatty liver disorder via coordinated modulation of the PPARα and INSIG/SREBP-1c pathways (68).

Previous studies highlighted SSD's protective effects against CCl₄-induced liver fibrosis (23,69-71), though detailed mechanisms were initially unclear. Recent research has provided deeper insights. In vitro experiments demonstrated that SSD induced apoptosis in HSC-T6 and LX-2 cells through both caspase-3-dependent and -independent pathways, promoting Bax and Bak translocation to mitochondria, which disrupts mitochondrial function and membrane potential, ultimately releasing apoptotic factors (72). Further investigations using TGF-β and CCl₄ to establish liver fibrosis models in vitro and in vivo revealed that SSD significantly reduced fibrosis markers Col-1 and α-SMA. Importantly, SSD inhibited fibrosis progression in primary HSCs and TGF-β-treated LX-2 cells by modulating the G protein-coupled estrogen receptor 1/autophagy pathway (73). An additional study noted that SSD attenuated oxidative stress-induced HSC-T6 activation and fibrosis progression through regulation of estrogen receptor β (Erβ), suggesting that SSD may act as a novel phytoestrogen with estrogen-like effects (31). Lin et al (32) demonstrated that SSD combats liver fibrosis via the ERβ/NLRP3 inflammasome (NLRP3, IL-18 and IL-1β) pathway. Further supporting this, Zhang et al (33) found that SSD reduces liver fibrosis by stimulating the ERβ pathway and downregulating the ROS/NLRP3 inflammasome. Collectively, these outcomes underscore SSD's strong potential as an anti-liver fibrosis agent.

FD ranks among the most prevalent digestive tract disorders. Zeng et al (74) developed a model to investigate SSD's impact on apoptosis, autophagy and the morphology of Cajal intestinal cells in FD. Their findings showed that SSD administration in FD rats prevented inflammatory cell infiltration, restored the normal gastric mucosal structure and significantly upregulated light chain 3 I/II, ghrelin and substance P (SP) protein expression, while reducing apoptosis rates. SSD also markedly improved the ultrastructure and clarity of intestinal Cajal cells (ICCs), suggesting it enhances ICC morphology, regulates excessive autophagy and alleviates gastrointestinal motility disorders in FD by modulating ghrelin and SP levels (74).

In a separate study on DSS-induced UC in mice, SSD significantly decreased pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and elevated mRNA levels of the anti-inflammatory cytokine IL-10 (75). The primary mechanism involves SSD's suppression of NF-κB activation and modulation of the gut microbiota to mitigate DSS-induced intestinal inflammation (75).

CP is a progressive fibro-inflammatory syndrome where acinar cell injury initiates inflammation and pancreatic stellate cell (PSC) activation (76). Cui et al (77) found that SSD alleviates pancreatic fibrosis by inhibiting PSC autophagy through the PI3K/AKT/mTOR pathway. Their subsequent research showed that SSD further reduces pancreatic injury by inhibiting acinar cell apoptosis and inflammation via the MAPK signaling pathway (37).

Prior research has shown that SSD can prevent aminonucleoside-induced proteinuria in rats (78). Another study indicated that SSD protects renal tubular epithelial cells from high-glucose-induced injury through modulation of SIRT3 (79). Li et al (51) demonstrated that SSD hinders the progression of mesangial proliferative glomerulonephritis in rats by downregulating TGF-β1 and reducing macrophages and CD8⁺ T lymphocytes. Additionally, it has been suggested that SSD reduces renal inflammation and apoptosis in a sepsis mouse model by inhibiting the transcription factor-7 (TCF7)/Fos-like antigen 1/matrix metalloproteinase (MMP)-9 axis (24), supporting its protective role in renal inflammation.

In CKD, skeletal muscle atrophy diminishes quality of life and increases morbidity and mortality (80). Huang et al (41) developed a muscle atrophy model using 5/6 nephrectomized mice and dexamethasone-treated C2C12 myotubes. Their results revealed that SSD activates the PI3K/AKT/Nrf2 pathway, reducing OS and alleviating CKD-induced muscle atrophy (41).

Cisplatin (DDP)-induced nephrotoxicity significantly limits the efficacy of this widely used anticancer drug (81), with inflammation and apoptosis likely contributing to the observed renal damage. Ma et al (82) examined the anti-apoptotic, anti-inflammatory and antioxidant effects of SSD in DDP-induced injury in human renal cortex and HK-2 human proximal tubular epithelial cells. Their findings indicated that SSD substantially increased the survival rate of DDP-treated HK-2 cells, improved nuclear morphology and reduced vesicle-3 activation and apoptosis. In addition, SSD treatment significantly lowered TNF-α, IL-1β and IL-6 secretion, NO generation and iNOS expression. The underlying mechanism suggests that SSD mitigates DDP-induced nephrotoxicity by inhibiting the MAPK and NF-κB signaling pathways (82).

Peritoneal dialysis has the potential to enhance life quality and prolong survival in patients with renal failure; however, peritoneal fibrosis can frequently lead to treatment discontinuation (83). Liu et al (84) found that SSD may alleviate peritoneal fibrosis in renal failure rats by modulating the TGF-β1/BMP7/Gremlin1/Smads pathway, though further research is needed to confirm SSD's mechanism in renal failure.

AD, a neurodegenerative disorder, manifests primarily through dementia, memory loss and language deficits (85). As elevated ROS levels are implicated in OS in AD (86). Du et al (87) showed that SSD alleviates glutamate-induced oxidative cytotoxicity in SH-SY5Y human neuroblastoma cells by activating the Nrf2 pathway, underscoring SSD's neuroprotective effects. However, it has been reported that SSD may impair cognitive function in mice by inhibiting hippocampal neurogenesis through the AKT/forkhead box G1 pathway (27). Another study found that SSD decreases the viability of neural stem/progenitor cells by disrupting neurotrophic factor receptor signaling, thus impairing hippocampal neurogenesis and potentially leading to cognitive deficits (88). These observations suggest a complex role for SSD in AD, with both protective and adverse effects, highlighting the need for further research to clarify SSD's impact on neurodegeneration.

Depression is a severe, recurrent disorder characterized by persistent low mood, anhedonia and impaired cognitive function (89). Early studies indicated that SSD therapy significantly increased hippocampal neurogenesis in rats exposed to unpredictable chronic mild stress (UCMS), as evidenced by elevated doublecortin levels. In addition, SSD treatment boosted hippocampal neuromolecule levels, such as p-CREB and BDNF, in UCMS rats, suggesting that SSD may counter CMS-induced depressive behaviors partly by enhancing hypothalamic-pituitary-adrenal axis function and supporting hippocampal neurogenesis (90). Further research demonstrated that SSD alleviates depressive-like behavior in UCMS rats by reducing NF-κB and microRNA (miR)-155, while upregulating the fibroblast growth factor 2 (91), homer protein homolog 1-metabotropic glutamate receptor 5 and mTOR signaling pathways (92). A recent study found that SSD alleviates depression in UCMS mice by promoting NLRP3 ubiquitination and suppressing inflammasome activation (26). SSD also reduced LPS-induced depression-like behavior in mice by inhibiting microglial activation and neuroinflammation, potentially through downregulation of the mammaglobin 1/Toll-like receptor 4/NF-κB pathway (93). These insights suggest SSD as a promising candidate for treating depressive disorders.

Diabetes complications include diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN) (94). Zhao et al (79) showed that SSD protects renal tubular epithelial cells (NRK-52E) from high glucose-induced OS by upregulating SIRT3, elucidating its protective mechanism against DN. Another study revealed that SSD improved body weight, lowered blood glucose levels, alleviated mechanical and thermal hyperalgesia, enhanced nerve conduction velocity and reduced pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in streptozotocin/HFD-induced DPN in rats. Of note, SSD mitigated DPN by inhibiting the aquaporin 1/Ras homolog family member A/Rho-associated protein kinase signaling pathway (25).

HT is an autoimmune condition (95). Du et al (45) reported that SSD therapy reduced lymphocyte infiltration in the thyroid tissue of HT mice, lowered reduced serum thyroid peroxidase antibody levels and suppressed the expression of Th1-type cytokine interferon-γ and Th17-type cytokine IL-17. SSD also shifted the M1/M2 macrophage balance in the spleen toward M2 polarization. These observations suggest that SSD could modulate Th1/Th2 and Th17/Treg imbalances and mitigate HT severity in murine models by promoting M2 macrophage differentiation (45).

Osteoarthritis is the most prevalent joint disease among the elderly, characterized by inflammation and autophagy dysregulation (96). A literature survey by Jiang et al (97) indicated that SSD may inhibit inflammation and modulate autophagic processes by downregulating the PI3K/AKT/mTOR signaling pathway, positioning SSD as a promising treatment option for osteoarthritis. Wu et al (98) demonstrated in their experimental investigation that SSD inhibited IL-1β-induced apoptosis in differentiated ATDC 5 chondrocytes in vitro. Furthermore, SSD effectively prevented cartilage degeneration in the knee joints of mice and reduced the number of osteochondrocytes in the subchondral bone. Of note, SSD activates the Nrf2/heme oxygenase-1/ROS axis, suppresses the production of inflammatory mediators and protects against ECM degradation, thereby delaying the progression of osteoarthritis in destabilization of the medial meniscus model mice (98). A recent study also reported that SSD reduces inflammatory responses in osteoarthritis mice and chondrocytes and mediates autophagy by upregulating miR-199-3p, which targets TCF4 (99). These insights collectively support the notion that SSD mitigates the development of osteoarthritis through its anti-inflammatory and autophagic effects.

In thyroid cancer, SSD has been shown to enhance p53 and Bax expression while reducing Bcl-2 levels, promoting apoptosis in thyroid cancer cells. In addition, SSD notably elevates p21 and inhibits cyclin-dependent kinase 2 and cyclin D1, leading to the suppression of human thyroid cancer cell growth (100).

Prior research has established that SSD inhibits growth and induces programmed cell death in non-small cell lung cancer (NSCLC) cells (A549 and H1299), primarily by inhibiting STAT3 phosphorylation and activating caspase 3 (52). Chen et al (46) further elucidated the anti-cancer mechanism of SSD, revealing that it induces apoptosis in A549 cells through two pathways: TGFα-JNK-p53 and TGFα-Rassfia-Mst1. SSD also inhibits A549 cell proliferation by activating two pathways: TGF-β-p53/p21/p27/p15/p16 and TGF-α/Rassfia/cyclin D1 (46). Drug resistance remains a significant challenge in lung cancer treatment (101). In vivo and in vitro studies by Tang et al (102) indicated that SSD reduced p-STAT3 levels and increased Bcl-2 expression. Downregulation of STAT3 enhanced lung cancer cell responsiveness to gefitinib, suggesting that the combination of SSD and gefitinib may yield improved anti-tumor effects in NSCLC cells, linked to the inhibition of the STAT3/Bcl-2 signaling pathway. Recent investigations have also demonstrated that SSD induces apoptosis in HCC827 and A549 NSCLC cells by increasing ROS levels and activating the NF-κB/NLRP3/caspase-1/gasdermin D pathway (50). These outcomes provide a strong rationale for the use of SSD in the treatment of NSCLC.

Elevated expression of P-glycoprotein (P-gp) in multidrug-resistant (MDR) cells poses a significant barrier to effective cancer chemotherapy (103). Research indicates that SSD effectively counteracts P-gp-mediated multidrug resistance in MCF-7/adriamycin breast cancer cells (104). Another study corroborated these findings, revealing that the combination of DOX and SSD yielded a stronger anti-cancer effect compared to either DOX or SSD alone (105). Furthermore, Wang et al (49) demonstrated that SSD significantly inhibits β-catenin and its associated downstream target genes, leading to programmed cell death in various triple-negative breast cancer cell lines (HCC1937, MDA-MB-468 and MDA-MB-231 and MCF-7). Fu et al (106) expanded on the mechanisms underlying SSD's anti-breast cancer activity, showing that it inhibits autophagosome-lysosome fusion and induces autophagy-independent apoptosis via caspase-3 activation in MDA-MB-231 cells. A recent untargeted metabolomic analysis highlighted that SSD exerts anti-breast cancer effects by regulating basal metabolism (107), with changes in serum metabolites observed in breast cancer mice following SSD treatment, including alterations in sphingolipid metabolism, glycerophospholipid metabolism and the biosynthetic pathways for phenylalanine, tyrosine and tryptophan (107).

Hepatocellular carcinoma (HCC) ranks among the most common malignancies (108). In an earlier study utilizing an diethyl nitrosamine (DEN)-induced rat HCC model, SSD was found to inhibit the expression of syndecan-2, MMP-2, MMP-13 and TIMP-2 in liver tissue, suggesting its potential anti-HCC effects (109). COX-2 (110) and C/EBPβ (111) are known to be associated with inflammation and carcinogenesis. One investigation revealed that SSD inhibited the proliferation of HCC SMMC-7721 cells and induced apoptosis by downregulating COX-2 expression and reducing prostaglandin E2 synthesis (112). In addition, SSD was shown to impede DEN-induced liver cancer in rats by suppressing C/EBPβ and COX-2 levels (113). Two further studies indicated that SSD inhibits COX-2 expression via the p-STAT3/HIF-1α pathway (114) and the p-STAT3/C/EBPβ signaling pathway (115), thereby exerting an anti-HCC effect.

The integration of SSD and radiotherapy demonstrates superior efficacy in the treatment of liver cancer compared to their individual applications. Research indicates that SSD enhances the radiosensitivity of SMMC-7721 liver cancer cells by regulating the G0/G1 and G2/M cell cycle checkpoints, which correlates with the upregulation of p53 and Bax and the downregulation Bcl-2 (116). A similar study confirmed that SSD also increases the radiosensitivity of liver cancer cells (SMMC-7721 and HepG2) under hypoxic conditions by suppressing hypoxia-inducible factor-1α, thereby triggering the upregulation of p53 and Bax and the downregulation of Bcl-2 (117). The activation of glioma-associated oncogene (GLI) family proteins and significant protein assimilation are characteristic of HCC cells. Hypoxia activates the sonic hedgehog pathway, which promotes epithelial-to-mesenchymal transition (EMT), invasion and chemosensitivity in HCC cells, with hypoxia-dependent GLI protein activation requiring SUMOylation (118-120). Zhang et al (121) demonstrated that SSD inhibited liver cancer cells (Hep3B) and enhanced chemotherapy sensitivity through sentrin-specific protease 5-dependent inhibition of Gli1 SUMOylation in hypoxic environments. Furthermore, SSD significantly increased radiation-induced apoptosis in SMMC-7721 and MHCC97L liver cancer cells while concurrently inhibiting cell proliferation (122). The introduction of the autophagy inhibitor chloroquine or the mTOR agonist MHY1485 attenuated the pharmacodynamic effects of SSD, suggesting that SSD enhances radiation-induced apoptosis in HCC cells by promoting autophagy through the inhibition of mTOR phosphorylation (123).

Ongoing investigations into the anti-HCC mechanisms of SSD have included a non-targeted metabolomics study revealing that SSD, in combination with neuropilin (NRP)-1 gene knockout, exerts anti-liver cancer effects in vitro, primarily by modulating lipid transport and phospholipid metabolism (124). In addition, the potential interactions between SSD and its hypothetic target, NRP-1, are under investigation. Li et al (125) found that SSD significantly induced the expression and enzyme activity of cytochrome P 450 enzyme (CYP)1A2 and CYP2D6 in HepaRG cells. Another study utilizing molecular docking indicated that SSD substantially suppressed the expression and enzyme activity of CYP3A4 protein in HepaRG cells; however, experimental validation is still required (126).

ICCA is a highly lethal malignant tumor, with systemic chemotherapy using gemcitabine as the primary clinical treatment option (127,128). Norepinephrine (NE) and epinephrine (E) have been shown to promote ICCA cell growth and diminish the efficacy of gemcitabine through stimulation of the β 2-adrenergic receptors (ADRB2) receptor (129). A 2023 study demonstrated that SSD can reverse the adverse effects of gemcitabine in ICCA cells by reducing ADRB2 levels. Furthermore, SSD inhibited drug efflux and glycolysis in ICCA cells by modulating the expression of multidrug resistance 1, ABC subfamily G, isoform 2 protein, hexokinase 2 and glucose transporter 1. This suggests that SSD may counteract NE- and E-induced gemcitabine resistance in intrahepatic cholangiocarcinoma via downregulation of ADRB2 and glycolytic signaling pathways (130).

GC remains a significant contributor to cancer-related mortality, with drug resistance being a critical factor in its poor prognosis (131). Research by Hu et al (28) indicated that SSD enhances the efficacy of DDP by inhibiting the growth and invasiveness of SGC-7901 and SGC-7901/DDP-resistant cells, thereby increasing DDP-induced apoptosis. SSD appears to enhance the sensitivity of GC cells to DDP, potentially through inhibition of the IKKβ/NF-κB pathway, which induces apoptosis and autophagy in GC cells (28). A recent network pharmacology study identified six key targets linking SSD to gastric cancer: VEGFA, IL-2, CASP3, BCL2L1, MMP2 and MMP1. Experimental results demonstrated that SSD induces apoptosis in cancer cells by enhancing caspase-3 activity and elevating Bcl-2 levels, while also inhibiting migration and invasion through upregulation of IL-2 and downregulation of MMP1 and MMP2 (132). These findings indicate that SSD may play a role in overcoming drug resistance in GC treatment.

Pancreatic cancer remains one of the deadliest malignancies with limited therapeutic options (133). SSD has been shown to inhibit the growth of pancreatic cancer cells (BxPC3, PANC1 and Pan02) and enhance the cleavage of apoptotic proteins caspase-3 and caspase-9 by activating the MAPK kinase 4-JNK signaling cascade (47). An additional in vivo and in vitro study found SSD directly suppresses pancreatic cancer cell apoptosis and invasion while modulating the immunosuppressive microenvironment to reactivate local immune responses. The primary mechanism involves reducing M2 macrophage polarization by downregulating phosphorylated STAT6 levels and the PI3K/AKT/mTOR signaling pathway (134). These findings suggest that SSD holds promise as a potential treatment for pancreatic cancer.

Cai et al (135) reported that SSD induces apoptosis in human renal cell adenocarcinoma cells (769-P and 786-O) by upregulating the p53 protein and arresting the cell cycle in the G0/G1 phase, primarily through inhibition of the EGFR/p38 signaling pathway.

PC ranks among the most prevalent malignancies affecting males (136). Research by Yao et al (137) demonstrated that SSD induces apoptosis in DU145 cells via the intrinsic apoptotic pathway. The primary mechanism involves SSD causing cell cycle arrest in G0/G1 phase through upregulation of p53 and p21, along with regulation of Bcl-2 family proteins, dissipation of mitochondrial membrane potential, release of cytochrome into the cytosol and activation of caspase-3, leading to apoptosis. Another study revealed that SSD suppresses the growth, migration and invasion of prostate cancer (DU145 and CWR22Rv1) by reversing EMT and inhibiting the expression and activity of MMP2/9 (138). In addition, SSD impedes the self-renewal capacity of cancer stem cell phenotypes by reducing glycogen synthase kinase 3β phosphorylation, thereby blocking the Wnt/β-catenin signaling pathway (138). These findings position SSD as a promising therapeutic agent for PC.

DDP and its derivatives serve as first-line anticancer drugs for ovarian cancer (139). Studies indicate that SSD sensitizes drug-resistant ovarian cancer cells to DDP-induced apoptosis by promoting mitochondrial fission and causing G2/M phase arrest. The specific mechanism involves the enhancement of calcium signaling, upregulating of mitochondrial fission proteins dynamin-related protein 1 and optic atrophy 1 and inhibition of MMPs (140).

Research conducted by Tang et al (141) revealed that SSD upregulates p21 and Cyclin B, leading to G2/M phase retention in endometrial cancer Ishikawa cells. Furthermore, SSD increased ROS levels, reduced the mitochondrial membrane potential, activated Bcl-2 and caspase family cascades, and mediated both endogenous and exogenous apoptosis pathways in Ishikawa cells. In addition, SSD influences three classic MAPK pathways (Ras/Raf/MEK/ERK, JNK and p38-MAPK pathways) to inhibit cell metastasis (141).

Although human osteosarcoma has a low incidence rate, its prognosis is often poor compared to other cancers (142). A study assessing SSD's therapeutic potential in osteosarcoma demonstrated that it significantly suppresses the proliferation of 143B and MG-63 cells. The underlying mechanism includes the upregulation of tumor protein 53 (p53) and its downstream targets (p21, p27, Bcl-2-like protein 4 and cleaved caspase-3), along with the downregulation of cyclin D1 expression levels (143). Another study within the same year indicated that SSD, either alone or in combination with the JNK inhibitor SP600125, inhibits proliferation, induces apoptosis, and suppresses migration and invasion in human osteosarcoma U2 cells. However, SP600125 alone did not show a significant effect on U2 cells. The mechanism involves enhancement of cytochrome release, elevation of the Bax/Bcl-2 ratio, and activation of caspases -3, -8 and -9, indicating that apoptosis is triggered via both mitochondrial and death receptor pathways (144). These findings provide a theoretical basis for the use of SSD in osteosarcoma treatment.

An earlier study demonstrated that SSD can inhibit apoptosis in human GBM U87 cells, primarily by significantly suppressing the phosphorylation of AKT and ERK while promoting the expression of phosphorylated JNK and cleaved caspase-3 (145). A subsequent investigation revealed that SSD notably impedes the growth of RG-2, U87-MG and U251 cells in a sugar-dependent manner, leading to a marked increase in the proportion of apoptotic cells. Further research has indicated that SSD induces apoptosis and autophagy by activating endoplasmic reticulum stress in GBM cells, thereby exerting anti-GBM effects (146). Chemotherapy remains a critical adjunctive treatment for glioblastoma; however, resistance to chemotherapy presents an urgent clinical challenge for neuro-oncologists (147). Liang et al (148) discovered that SSD partially suppressed the migration, invasion and apoptosis of LN-229 cells. When combined with temozolomide (TMZ), SSD enhanced the chemotherapeutic efficacy of TMZ by increasing the apoptosis rate and LDH release in LN-229 cells, while also inhibiting the expression of stem cell factors (octamer-binding transcription factor 4, SRY-box transcription factor 2, myelocytomatosis viral oncogene homolog and Kruppel-like factor 4 at both gene and protein levels (148). These insights lay the groundwork for the potential application of SSD in overcoming GBM chemotherapy resistance, although further research is required for a more comprehensive understanding.

MB is a highly malignant embryonic tumor and the most common primary tumor of the posterior fossa in children (149). A 2021 study demonstrated that SSD inhibits tumor progression in MB-transplanted mice by suppressing the Hedgehog signaling pathway (150). However, further investigations are necessary to elucidate the mechanisms underlying SSD's anti-MB effect.

AML remains an uncommon but potentially devastating condition with persistently elevated mortality rates (151). The fat mass and obesity-associated protein (FTO), an mRNA N6-methyladenosine (m6A) demethylase, functions as an oncogene that facilitates leukemic oncogene-driven cellular transformation and leukemogenesis (152,153). Research by Sun et al (154) demonstrated that SSD significantly suppressed AML cell proliferation, induced apoptosis and caused cell cycle arrest both in vivo and in vitro. At the molecular level, SSD specifically targets FTO, thereby enhancing m6A RNA methylation, which reduces the stability of downstream gene transcripts and inhibits associated pathways. Notably, SSD also mitigates FTO/m6A-mediated resistance to tyrosine kinase inhibitors in leukemia (154). This investigation reveals promising therapeutic avenues for the treatment of leukemia.