DNA polymerases (α, β, and Δ) and DNA topoisomerase II. [4]
Potassium channels (KATP channels). [4]
Angiotensin II receptor. [4]
Pregnane X receptor (PXR) and aryl hydrocarbon receptor (AHR). [4]

In isolated aortic rings with or without endothelium, isosteviol ((-)-Isosteviol) dose-dependently reduces vasopressin (10-8 M)-induced vasoconstriction. On arterial strips, however, the vasodilatory action of isosteviol vanished in the presence of potassium chloride (3×10-2 M). In isolated aortic rings contracted by 10-8 M vasopressin, the vasodilatory effects of isosteviol were blocked only by specific inhibitors of ATP-sensitive potassium (KATP) channels or small-conductance calcium-activated potassium (SKCa) channels [1]. Karebutoxin did not counteract the attenuating impact of isosteviol on the vasopressin- and phenylephrine-induced increase in [Ca2+]i. Glyburide, apamine, and 4-aminopyridine did, however. Moreover, the inhibitory impact of isosteviol on [Ca 2+]i was prevented when A7r5 cells were co-treated with glyburide, apamin, and 4-aminopyridine [2]. DNA synthesis and endothelin-1 secretion caused by angiotensin II are inhibited by isosteviol (1-100 micromol/l). Angiotensin II-induced intracellular reactive oxygen species were shown to be inhibited by isosteviol by the use of 2'7'-dichlorofluorescein diacetate, a redox-sensitive fluorescent dye [3].

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Isosteviol and its derivatives exhibited cytotoxic activity against various human cancer cell lines. A compound with an exo-methylene cyclopentanone structure displayed significant cytotoxic activity with IC₅₀ values ranging from 0.09 to 5.71 μM against several human cancer cell lines, with most derivatives showing superior cytotoxicity compared to doxorubicin. [4]
Carbothioamide-substituted pyrazole derivatives of isosteviol showed potent cytotoxicity against Raji cell lines with an IC₅₀ value of 6.51 μM. [4]
An oxadiazole ring-containing isosteviol derivative exhibited the strongest effect against hepatocellular liver carcinoma (HepG2) and highly metastatic melanoma (B16F10) cells with an IC₅₀ of 0.02 μM. [4]
An isosteviol analogue (number 10-C) inhibited apoptosis in HepG2 cells with an IC₅₀ of 2 μM. [4]
MOM-ether analogs of isosteviol displayed potent activity against H1299 lung cancer cell lines with IC₅₀ values of 14 and 21 μM, while showing reduced cytotoxic effects on NL-20 normal lung epithelial cells. [4]
Isosteviol exhibited inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). [4]
Isosteviol acts as an α-glucosidase inhibitor. [4]
Isosteviol inhibited angiotensin-II-induced cell proliferation and endothelin-1 secretion, reactive oxygen species (ROS) generation, and suppressed extracellular signal-regulated kinase (ERK) phosphorylation in vascular smooth muscle cells. It also inhibited DNA synthesis and endothelin-1 secretion in angiotensin-II-stimulated rat aortic smooth muscle cells. [4]
Isosteviol relaxed vasopressin-induced vasoconstriction in isolated aortic rings with or without endothelium in a dose-dependent manner. This vasodilator effect was markedly reduced in the presence of glibenclamide, a KATP channel blocker. [4]
Isosteviol exhibited vasorelaxant activity. One biotransformation metabolite showed a 17-fold increase in vasorelaxant activity compared to the parent compound. [4]
Biotransformation of isosteviol by fungi yielded metabolites such as 7α-hydroxyisosteviol, 11α-hydroxyisosteviol, 12α-hydroxyisosteviol, 17-hydroxyisosteviol, and 7-oxoisosteviol, all of which exhibited more potent inhibitory effects on EBV-EA activation than the parent compound. [4]
Isosteviol and its derivatives with onium nitrogen atoms displayed efficient antibacterial properties. [4]
Conjugates of isosteviol with adipic acid dihydrazide showed maximal inhibitory effect against Mycobacterium tuberculosis H37Rv with a MIC of 1.7 and 3.1 μg/mL. [4]
An isosteviol macrocyclic glycoterpenoid with two isosteviol moieties and two glucosamine residues inhibited the in vitro growth of M. tuberculosis H37Rv with a MIC value of 12.5 μg/mL. [4]
Isosteviol derivatives with a dodecamethylene spacer between two quaternized nitrogen atoms exhibited the greatest antimicrobial activity. [4]
Isosteviol and its derivatives were found to be α-glucosidase inhibitors. [4]

Isosteviol stimulated leaf growth and delayed root development in winter wheat cultivar Mironovskaya 808 at an optimum concentration of 10⁻⁸ M. It also increased the activity of soluble lectins and enhanced frost resistance in non-hardened plants. [4]
In lettuce hypocotyl bioassays, isosteviol was more active than gibberellic acid at concentrations < 10⁻⁹ M. [4]
In spontaneously hypertensive rats, isosteviol administered via intraperitoneal injection demonstrated antihypertensive effects through calcium influx inhibition in vascular smooth muscle cells. [4]
In an isolated guinea pig heart model of myocardial ischemia-reperfusion (IR) injury, pretreatment with isosteviol (50, 250, or 500 nmol) significantly decreased cardiac dysfunction (p < 0.05). The protective effect was partially antagonized by the mito-KATP blocker 5-HD. [4]
In a rat model of focal cerebral ischemia induced by middle cerebral artery occlusion, pretreatment with isosteviol alleviated ischemia-reperfusion damage, reduced cell death, inflammation, and infarct volume. Isosteviol sodium (STVNa) treatment significantly reduced neurobehavioral impairment. [4]
In Zucker diabetic fatty (ZDF) rats, isosteviol significantly decreased plasma glucose levels in the intravenous glucose tolerance test. [4]
In KKAy diabetic mice, isosteviol increased insulin sensitivity and decreased insulin resistance. The glucose-insulin index was 6.9 for the isosteviol (ISV) group compared to 1.6 for the KKAy control, indicating reduced insulin resistance. [4]
In a mouse model of arsenic toxicity, dihydroxy-isosteviol-methyl-ester (DIME) reversed arsenic-induced cellular dysfunction in the testis. [4]

For cytotoxic activity evaluation, various human cancer cell lines (including SGC 7901, A549, Raji, HeLa, B16-F10, HepG2, Bel-7402, U251, MCF-7, MDA-MB-231, HCT116, Huh7, SW620, and H1299) and normal cell lines (NL-20, MRC-5) were used. Cell viability was assessed to determine IC₅₀ values. [4]
For anti-inflammatory activity, RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS). The levels of TNF-α and COX-2 mRNA were measured to assess the anti-inflammatory effects of isosteviol derivatives. [4]
For antiviral activity, Huh7 cells expressing replicating HBV were used to evaluate inhibition of viral gene expression and encapsulated viral DNA intermediates. [4]
For α-cell function studies, α-TC1-6 cells were cultured with 0.5 mM palmitate and 18 mM glucose for 72 hours. Glucagon release and triglyceride content were measured. Isosteviol at 10⁻⁸ and 10⁻⁶ M reduced palmitate-stimulated glucagon release by 27%. [4]
For angiotensin II antagonist studies, rat aortic smooth muscle cells were preincubated with isosteviol and then stimulated with angiotensin II. [³H]-thymidine incorporation and endothelin-1 secretion were analyzed. [4]

Plant growth regulator study: Winter wheat cultivar Mironovskaya 808 was cultivated under a 12-hour photoperiod with 100 W/m² light intensity at 23°C. Isosteviol was applied at an optimum concentration of 10⁻⁸ M. [4]
Antihypertensive study: Isosteviol was administered via intraperitoneal injection to spontaneously hypertensive rats. [4]
Cardioprotection study: Isolated guinea pig hearts were subjected to ischemia followed by reperfusion. Pretreatment with isosteviol at concentrations of 50, 250, or 500 nmol was performed. [4]
Neuroprotection study: Focal cerebral ischemia was induced by middle cerebral artery occlusion in rats. Isosteviol sodium (STVNa) was administered via injection. Infarct volume and neurobehavioral impairment were assessed. [4]
Anti-hyperglycemia study: Zucker diabetic fatty (ZDF) rats were fasted for 12 hours before infusion of isosteviol and glucose. Blood samples were taken at different time intervals, and glucose concentration was measured using the glucose oxidase method; plasma insulin concentration was determined by radioimmunoassay. [4]
Diabetes study: KKAy diabetic mice were fed an anti-diabetic diet containing isosteviol for 9 weeks. [4]

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Plant growth regulator study: Winter wheat cultivar Mironovskaya 808 was cultivated under a 12-hour photoperiod with 100 W/m² light intensity at 23°C. Isosteviol was applied at an optimum concentration of 10⁻⁸ M. [4]
Antihypertensive study: Isosteviol was administered via intraperitoneal injection to spontaneously hypertensive rats. [4]
Cardioprotection study: Isolated guinea pig hearts were subjected to ischemia followed by reperfusion. Pretreatment with isosteviol at concentrations of 50, 250, or 500 nmol was performed. [4]
Neuroprotection study: Focal cerebral ischemia was induced by middle cerebral artery occlusion in rats. Isosteviol sodium (STVNa) was administered via injection. Infarct volume and neurobehavioral impairment were assessed. [4]
Anti-hyperglycemia study: Zucker diabetic fatty (ZDF) rats were fasted for 12 hours before infusion of isosteviol and glucose. Blood samples were taken at different time intervals, and glucose concentration was measured using the glucose oxidase method; plasma insulin concentration was determined by radioimmunoassay. [4]
Diabetes study: KKAy diabetic mice were fed an anti-diabetic diet containing isosteviol for 9 weeks. [4]

[1]. Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat. Life Sci. 2004 Mar 26;74(19):2379-87.

[2]. Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. Planta Med. 2004 Feb;70(2):108-12.

[3]. Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells. Pharmacology. 2006;76(4):163-9.

[4]. Bioactivity Profile of the Diterpene Isosteviol and its Derivatives. Molecules. 2019 Feb 14;24(4):678.

Isosteviol is a diterpenoid compound. It has been reported that Isosteviol has been detected in red stevia (Ceriops decandra), and relevant data are available. See also: Stevia rebaudiuna leaves (partial).

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Isosteviol (ent-16-oxobeyran-19-oic acid) is a tetracyclic diterpenoid obtained through acid-catalyzed hydrolysis of stevioside, a natural sweetener from Stevia rebaudiana. It exhibits a wide spectrum of pharmacological activities, including anti-inflammatory, antihypertensive, immunoregulatory, antiviral, antibacterial, and anticancer properties. Isosteviol is a metabolite of stevioside and has been approved by European food safety authorities and other regulatory bodies. It serves as a useful building block in organic synthesis and has potential applications as a plant growth regulator. [4]

C20H30O3

318.46

318.219

27975-19-5

27975-19-5 (free acid);1160958-41-7 (sodium);

99514

White to off-white solid powder

1.2±0.1 g/cm3

455.6±38.0 °C at 760 mmHg

228.0 to 232.0 °C

243.5±23.3 °C

0.0±2.4 mmHg at 25°C

1.551

4.13

1

3

1

23

583

6

O=C1C([H])([H])[C@]23C([H])([H])C([H])([H])[C@]4([H])[C@@](C(=O)O[H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@@]4(C([H])([H])[H])[C@]2([H])C([H])([H])C([H])([H])[C@@]1(C([H])([H])[H])C3([H])[H]

KFVUFODCZDRVSS-XGBBNYNSSA-N

InChI=1S/C20H30O3/c1-17-9-5-14-18(2)7-4-8-19(3,16(22)23)13(18)6-10-20(14,12-17)11-15(17)21/h13-14H,4-12H2,1-3H3,(H,22,23)/t13-,14-,17-,18+,19+,20-/m0/s1

(1R,4S,5R,9S,10R,13S)-5,9,13-trimethyl-14-oxotetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylic acid

NSC-231875 NSC231875 (−)-IsosteviolIsosteviol, NSC 231875

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~314.02 mM)

Solubility in Formulation 1: ≥ 2.75 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.75 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.75 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)