Isobavachalcone / GSH Cancer Research Results

IBC, Isobavachalcone: Click to Expand ⟱
Features:

Isobavachalcone - Prenylated Chalcone

Type: Natural prenylated chalcone / flavonoid-related phytochemical
-Chalcone → chemical class / parent scaffold, not a molecular target. -Example Chalones: Isobavachalcone, xanthohumol, licochalcone A, isoliquiritigenin

Sources: Found in several medicinal plants, particularly Psoralea corylifolia (Cullen corylifolium), as well as other plant species containing prenylated chalcones.

Function: Isobavachalcone is a bioactive prenylated chalcone with anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective activities. Reported molecular effects include modulation of AKT, ERK/MAPK, ROS, apoptosis, inflammatory signaling, and cellular stress pathways.

Cancer: Experimental studies demonstrate inhibition of cancer-cell proliferation, migration, and invasion and induction of apoptosis and other forms of regulated cell death. IBC can suppress AKT and ERK signaling, increase tumor-cell oxidative stress, and modulate antitumor immune responses. Anticancer activity has been demonstrated in pancreatic, breast, oral, colorectal, thyroid, and other experimental cancer models.

Alzheimer's Disease: Preclinical studies indicate neuroprotective activity, including reduction of Aβ accumulation and plaque pathology, suppression of neuroinflammation, and improvement of memory and cognitive deficits in Alzheimer's disease models.

Isobavachalcone — Isobavachalcone (IBC; CAS 20784-50-3) is a naturally occurring prenylated chalcone and flavonoid-related phytochemical found particularly in Psoralea corylifolia L. (syn. Cullen corylifolium; Psoraleae Fructus/Bu Gu Zhi). It is an experimental small-molecule natural product with anticancer, anti-inflammatory, antimicrobial, and neuroprotective activities. Current anticancer evidence is preclinical and increasingly supports direct or proximal effects on SIRT2, DHODH, thioredoxin reductase 1, AKT signaling, mitochondrial function, and redox homeostasis. IBC has not been established as an approved anticancer or Alzheimer therapy.

Primary mechanisms (ranked):

  1. Mitochondrial and redox disruption with ↑ ROS, mitochondrial membrane depolarization, impaired respiration/ATP production, mitochondrial Ca²⁺ overload, and activation of mitochondrial permeability-transition-associated cell death.
  2. ↓ AKT signaling, including direct inhibition of AKT1 activity in early studies and suppression of AKT phosphorylation, reducing survival signaling and promoting mitochondrial apoptosis.
  3. Direct ↓ SIRT2 activity, disrupting SIRT2/α-tubulin signaling and downstream STAT3/c-Myc and Snail/MMP pathways in triple-negative breast cancer.
  4. ↓ DHODH with mitochondrial dysfunction, mtDNA release, ↑ ROS, and activation of cGAS-STING-associated antitumor immunity in gastric cancer models.
  5. ↓ thioredoxin reductase 1, weakening cellular thioredoxin antioxidant capacity and promoting ROS-dependent ER stress and apoptosis in prostate cancer.
  6. Induction of multiple regulated cell-death programs including mitochondrial apoptosis, non-canonical mitochondrial permeability-transition-driven necrosis, pyroptosis, necroptosis, and autophagy, depending on tumor model.
  7. Suppression of invasion and metastatic signaling through pathways including ↓ β-catenin, ↓ MMP-2/MMP-9, ↓ Snail, and other context-dependent AKT/GSK-3β/β-catenin and SIRT2-associated mechanisms.
  8. Antitumor immune modulation, including ↑ CD8+ T-cell infiltration, ↓ M2 macrophage polarization, and STING-associated innate immune activation in animal tumor models.
  9. ABCB1 modulation and membrane perturbation, potentially increasing drug accumulation in some multidrug-resistant cancer cells.
  10. Secondary NRF2/HO-1 activation has been reported primarily in anti-inflammatory/non-cancer contexts and should not be interpreted as the principal anticancer mechanism.

Bioavailability / PK relevance: Human pharmacokinetics have not been established. Rat oral pharmacokinetic studies demonstrate measurable systemic exposure after high oral dosing, but IBC undergoes extensive glucuronidation involving UGT1A1, UGT1A3 and additional UGT isoforms, with BCRP/MRP-mediated glucuronide efflux. These metabolic characteristics may limit free systemic exposure. IBC also inhibits multiple CYP and UGT enzymes in vitro at low-micromolar concentrations, creating a potential drug-interaction concern if therapeutically relevant human exposure can be achieved.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately low- to several-tens-of-micromolar IBC concentrations; for example, MCF-7 growth inhibition has been reported at IC50 values around 28–38 µM, whereas direct SIRT2 inhibition occurs at substantially lower concentrations with an enzymatic IC50 of approximately 0.84 µM. Human plasma concentrations after oral dosing are unknown, so it cannot currently be assumed that the concentrations required for many cell-culture anticancer effects are clinically achievable. High-concentration mitochondrial ROS effects are particularly relevant to the hepatotoxicity signal and may narrow any therapeutic window.

Clinical evidence status: Preclinical. Anticancer activity has been demonstrated in numerous cancer cell systems and several mouse xenograft/allograft models, including breast, gastric, pancreatic, colorectal, prostate, AML, thyroid, and other cancers. No established human anticancer efficacy, therapeutic dose, validated exposure-response relationship, or regulatory approval has been demonstrated.

Safety: Hepatotoxicity is a significant translational constraint. IBC itself has produced mitochondrial dysfunction, ROS accumulation, loss of mitochondrial membrane potential, ATP depletion, apoptosis, and ferroptosis-associated injury in hepatic experimental systems. Psoralea corylifolia preparations are independently associated with clinically reported liver injury, although toxicity of the whole herb cannot be attributed exclusively to IBC. Potential CYP/UGT inhibition further raises concern for pharmacokinetic drug interactions.

Isobavachalcone Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 Mitochondrial ROS and bioenergetic disruption ↑ ROS; ↓ mitochondrial membrane potential; ↓ respiration; ↓ ATP Similar mitochondrial toxicity can occur in hepatocytes Metabolic collapse and cell death Central recurring mechanism across multiple cancer models, but lack of strict tumor selectivity is an important safety limitation.
2 AKT survival signaling ↓ AKT activity; ↓ p-AKT ↓ p-AKT reported during hepatic toxicity ↓ survival signaling; ↑ apoptosis IBC has been reported to inhibit AKT1 kinase and repeatedly suppress cellular AKT phosphorylation.
3 Mitochondrial permeability transition and Ca²⁺ ↑ mitochondrial Ca²⁺; ↑ pore opening; ↓ membrane potential Not well characterized ↑ regulated necrosis ROS-dependent non-canonical mitochondrial permeability-transition-driven necrosis demonstrated in breast and lung cancer models.
4 SIRT2 signaling ↓ SIRT2; ↑ α-tubulin acetylation; ↓ STAT3/c-Myc; ↓ Snail/MMP signaling Limited comparative data ↓ proliferation and migration; ↑ apoptosis Direct SIRT2 inhibition reported with an enzymatic IC50 of approximately 0.84 µM in TNBC studies.
5 DHODH mitochondrial pyrimidine metabolism ↓ DHODH; ↑ ROS; ↑ mitochondrial damage; ↑ mtDNA release Limited comparative data Metabolic stress and antitumor immune activation Recent gastric-cancer evidence identifies DHODH as a functional target linking mitochondrial injury with STING signaling.
6 cGAS-STING innate immune signaling ↑ STING-associated signaling Context-dependent ↑ antitumor immune response Associated with mitochondrial damage and mtDNA release in gastric-cancer models.
7 Thioredoxin reductase 1 redox defense ↓ TrxR1; ↑ ROS; ↑ ER stress Potential oxidative toxicity ↑ apoptosis TrxR1 has been proposed as a direct redox-sensitive IBC target in prostate cancer cells.
8 Mitochondrial apoptosis ↑ Bax; ↓ Bcl-2/Bcl-xL/Mcl-1; ↑ cytochrome c; ↑ caspase-9/3; ↑ PARP cleavage Can also occur in hepatic cells ↑ apoptosis Highly reproducible downstream phenotype in several tumor types.
9 Pyroptosis ↑ caspase-dependent GSDME cleavage Insufficient comparative data ↑ inflammatory cell death Demonstrated particularly in anaplastic thyroid cancer models.
10 Necroptosis and autophagy ↑ RIP3/MLKL signaling; ↑ LC3-II/I (model-dependent) Context-dependent Multiple regulated cell-death responses Observed in selected breast-cancer models; not a universal IBC response.
11 AKT GSK-3β β-catenin signaling ↓ pathway activity Not well characterized ↓ proliferation and survival Reported prominently in colorectal cancer cells.
12 Migration and extracellular matrix remodeling ↓ MMP-2; ↓ MMP-9; ↓ Snail; ↓ migration/invasion Limited data ↓ invasive phenotype Supported in oral, breast, colorectal, and related cancer models.
13 Tumor immune microenvironment ↑ CD8+ T cells; ↓ M2 macrophages Immune modulation is context-dependent ↑ antitumor immunity Demonstrated in orthotopic pancreatic tumor models.
14 ABCB1 multidrug resistance ↓ ABCB1 transport function (context-dependent) May alter xenobiotic transport Potential chemosensitization IBC behaves as a membrane-active ABCB1 substrate and/or competitive inhibitor; clinical chemosensitization has not been established.
15 NRF2 HO-1 antioxidant signaling Context-dependent ↑ NRF2/HO-1 reported mainly in inflammatory models Anti-inflammatory and cytoprotective effects Secondary mechanism and potentially opposite to the desired pro-oxidant anticancer state.
16 Clinical Translation Constraint Effective concentrations frequently in low-to-tens-of-µM range Hepatic mitochondrial and ferroptotic toxicity documented experimentally Limits therapeutic translation Human PK, therapeutic exposure, tumor selectivity, maximum tolerated dose, and clinical efficacy remain undefined; extensive glucuronidation and CYP/UGT interactions are additional constraints.

Alzheimer's disease relevance: Isobavachalcone has meaningful but exclusively preclinical evidence in Alzheimer's disease. In transgenic AD mouse models, IBC has improved memory-related outcomes and reduced Aβ pathology, tau hyperphosphorylation, and neuroinflammation. More recent work links these effects to ↑ autophagic Aβ clearance and ↓ NLRP3 inflammasome activation in astrocytes. Earlier studies also identified inhibitory activity against several AD-associated targets, including Aβ42-related processes, BACE1, GSK-3β, and acetylcholinesterase. No human efficacy, dose, pharmacokinetic target, or clinical safety data support its use for AD.

Isobavachalcone Alzheimer-Relevant Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Amyloid beta clearance ↓ Aβ accumulation and plaque burden Reduced amyloid pathology Supported in transgenic mouse models.
2 Autophagy ↑ autophagic clearance ↑ Aβ removal Mechanistically supported in primary astrocytes and 5xFAD mice.
3 NLRP3 inflammasome ↓ NLRP3 activation ↓ neuroinflammation Astrocyte-associated anti-inflammatory mechanism demonstrated in recent preclinical work.
4 Tau pathology ↓ tau hyperphosphorylation and filament formation Reduced tau pathology Reported in 3×Tg-AD mice.
5 GSK-3β ↓ activity Potential reduction of tau phosphorylation Supported mainly by earlier multi-target biochemical studies.
6 BACE1 and amyloidogenic processing ↓ activity Potential ↓ Aβ generation Preclinical biochemical evidence; in-vivo contribution is less certain.
7 Acetylcholinesterase ↓ activity Potential cholinergic support Biochemical activity; clinical relevance has not been established.
8 Clinical Translation Constraint Human exposure and CNS penetration not established Uncertain therapeutic feasibility Potential hepatotoxicity, metabolism, drug interactions, and lack of human PK/efficacy are major constraints.


GSH, Glutathione: Click to Expand ⟱
Source:
Type:
Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress.
Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system.
cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment.
While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied.
Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy.
Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death.
Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion.
Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS).

"...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..."
"Cancer cells have a high level of GSH compared to normal cells."
"...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy."

The loss of GSH is broadly known to be directly related to the apoptosis progression.
Scientific Papers found: Click to Expand⟱
7803- IBC,    Isobavachalcone induces hepatotoxicity in zebrafish embryos and HepG2 cells via the System Xc--GSH-GPX4 signaling pathway in ferroptosis response
- in-vivo, Nor, NA - in-vitro, NA, HepG2
*hepatoP↓, *ALAT↑, *AST↑, *ROS↑, *MDA↑, *Catalase↓, *GSH↓, *GPx↓, *i-Iron↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   GPx↓, 1,   GSH↓, 1,   i-Iron↑, 1,   MDA↑, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↑, 1,   AST↑, 1,  

Functional Outcomes(tgid=23) ⓘ

hepatoP↓, 1,  
Total Targets: 10

Scientific Paper Hit Count for: GSH, Glutathione
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:446  Target#:137  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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