Synonym name:
Catalogue No.: BP0831
Cas No.: 52659-56-0
Formula: C₂₀H₃₄O₄
Mol Weight: 338.488
Botanical Source: Siegesbeckia pubescens and Siegesbeckia glabrescens

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

Description:

Kirenol possesses anti-bacteria, immunosuppression, anti-obesity, anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. Kirenol has significant potential for its discovery as a new lead compound for management of topical pain and inflammation; it can upregulate nuclear Annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats. Kirenol can attenuate experimental autoimmune encephalomyelitis by inhibiting differentiation of Th1 and th17 cells and inducing apoptosis of effector T cells. Kirenol activates the BMP and Wnt/β-catenin signaling pathways.

References:

Sci Rep. 2015 Mar 12;5:9022.    

Kirenol attenuates experimental autoimmune encephalomyelitis by inhibiting differentiation of Th1 and th17 cells and inducing apoptosis of effector T cells.   

Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is characterized by CNS demyelination mediated by autoreactive T cells. Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has potent anti-inflammatory activities. 

METHODS AND RESULTS:

Here we investigated effects of Kirenol on EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical scores in EAE mice. Kirenol treatment reduced expression of IFN-γ and IL-17A in the serum and proportion of Th1 and Th17 cells in draining lymph nodes. Priming of lymphocytes was reduced and apoptosis of MOG-activated CD4+ T cells was increased in Kirenoltreated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further in vitro studies showed that Kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD4+ T cells in a dose- and time-dependent manner. Kirenol treatment upregulated Bax,downregulated Bcl-2,and increased activation of caspase-3 and release of cytochrome c, indicating that a mitochondrial pathway was involved in Kirenol induced apoptosis. Moreover, pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific caspase 3 inhibitor Ac-DEVD-CHO in lymphocytes reduced Kirenol induced apoptosis. 

CONCLUSIONS:

Our findings implicate Kirenol as a useful agent for the treatment of MS.    

Pharmacogn Mag. 2012 Apr;8(30):149-55.    

Kirenol production in hairy root culture of Siegesbeckea orientalis and its antimicrobial activity.   

Despite the excellent anti-inflammatory and anti-rheumatic efficacy associated with Kirenol generation, the content of Kirenol in Siegesbeckea orientalis is quite low. This study was designed to establish a reliable Kirenol production protocol by transformed root cultures of S. orientalis and to investigate the antimicrobial activities of Kirenol, hairy root, and S. orientalis. 

METHODS AND RESULTS:

Transformed root cultures of S. orientalis were established by the transformation of Agrobacterium rhizogenes A4. Transgenic status of the roots was confirmed by polymerase chain reaction (PCR) using rolB specific primers. The biomass and Kirenol accumulation of hairy root clones were assessed using four different culture media: MS, MS/2, B5, and white. The antimicrobial activities of Kirenol, hairy root, and S. orientalis were evaluated by the disc diffusion method. The optimum media for Kirenol synthesis was MS. The content of Kirenol in transformed hairy roots made up about 80% of that observed in natural leaves of S. orientalis (1.6 mg/g dry weight). All tested samples displayed antimicrobial activity against Gram-positive pathogens including Staphylococcus epidermidis, Staphylococcus aureus, and Acinetobacter baumannii, with MIC ranging from 78 to 625 μg/mL. 

CONCLUSIONS:

The high level of Kirenol contents was obtained from hairy roots of S. orientalis. Kirenol was effective against gram-positive bacteria. Interestingly, the extract from hairy roots showed a diverse antimicrobial effect from that of Kirenol and S. orientalis.    

J Ethnopharmacol. 2011 Oct 11;137(3):1089-94.    

Topical anti-inflammatory and analgesic activity of kirenol isolated from Siegesbeckia orientalis.   

Siegesbeckia orientalis has been traditionally used as a topical anti-inflammatory and analgesic agent. Current study was designed to explore the topical anti-inflammatory and analgesic effects of a constituent isolated from Siegesbeckia orientalis (Compositae), in order to validate its folk use. 

METHODS AND RESULTS:

Kirenol was isolated from ethanolic extract of Siegesbeckia orientalis. Several topical formulations containing Kirenol were investigated for anti-inflammatory and analgesic activities in rat. The effects were studied using carrageenan-induced rat acute inflammation model, complete Freund's adjuvant (CFA)-induced chronic inflammation and formalin test in rats. Piroxicam gel and methyl salicylate ointment were studied as positive control for anti-inflammatory and analgesic activity, respectively. The anti-inflammatory effect of Kirenol 0.4-0.5% (w/w) was similar to the effect of piroxicam gel 4h after carrageenan injection. The analgesic activity of topical preparation with more than 0.4% (w/w) was observed in the late phase. These effects may be due, at least in part, to the pro-inflammatory cytokine production of IL-1β and TNF-α. The administration of Kirenol cream at the dose of 0.3, 0.4 and 0.5% (w/w) significantly inhibited the development of joint swelling induced by CFA, which was auxiliary supported by histopathological studies. 

CONCLUSIONS:

Kirenol has demonstrated its significant potential to be further investigated for its discovery as a new lead compound for management of topical pain and inflammation, although further pharmacological research is necessary to fully understand its mechanism of action. It also supports the potential beneficial effect of topically administered Siegesbeckia orientalis in inflammatory diseases.    

Phytomedicine. 2012 Jul 15;19(10):882-9.    

Kirenol exerts a potent anti-arthritic effect in collagen-induced arthritis by modifying the T cells balance.   

Rheumatoid arthritis is characterized by the imbalance of T cells, which leads to increased pro-inflammatory and reduced anti-inflammatory cytokines. Modulating the balance among T cells is crucial for the treatment of RA. Kirenol is a major diterpenoid components of Herba Siegesbeckiae, which has been applied for arthritic therapy for centuries. Since prior research showed Kirenolexhibited anti-inflammatory effect in rats, in this study we have evaluated the effect and mechanism of bioactive Kirenol in a rat model of collagen-induced arthritis (CIA) on modulation of T cells. 

METHODS AND RESULTS:

After immunization with bovine type II collagen (CII), Wistar rats were orally administered saline (CIA group), 2 mg/kg Kirenol or 2 mg/kg prednisolone daily for 30 days. The severity of arthritis was clinically and histologically assessed. The numbers of CD4⁺CD25⁺Foxp3⁺ T regulatory cells (Tregs) and IFNγ⁺CD4⁺ and IL4⁺CD4⁺ T cells were determined by flow cytometry, the mRNA expression level of Foxp3 was quantified by RT-PCR, cytokine levels were measured by ELISA and CII-induced cell proliferation was quantified in vitro. Kirenol significantly delayed the occurrence and reduced the disease severity of CIA. Histological analysis confirmed Kirenol suppressed joint inflammation and inhibited cartilage and bone destruction, compared to the CIA group. Kirenol also upregulated the mRNA expression of Foxp3, increased the numbers of CD4⁺CD25⁺Foxp3⁺ and IL4⁺CD4⁺ T cells, and reduced the number of IFNγ⁺CD4⁺ T cells. Kirenol reduced the levels of TNF-α, IL-17A and IL-6 in synovial fluid and TNF-α, IL-17A and IFN-γ in serum, and increased the serum levels of IL-4, IL-10 and TGF-β1. In addition, Kirenol inhibited the ability of CII to induce splenocyte, PBMC and lymph node cell proliferation in vitro, compared to cells from CIA rats. 

CONCLUSIONS:

In conclusion, these results suggest that Kirenol may be a potential immunosuppressant for the treatment for rheumatoid arthritis.    

HPLC of Kirenol

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Kirenol is a diterpenoid compound derived from natural plants, which has recently attracted widespread attention due to its multi-target and multi-mechanism pharmacological activity. As an orally active cell apoptosis inducer and signaling pathway regulator, Chirenol demonstrates significant biological effects in anti-tumor, anti-inflammation, anti-fibrotic, and various chronic disease models. Its mechanisms of action include apoptosis, autophagy, regulation of oxidative stress, and regulation of multiple cellular signaling pathways, especially targeting the protein kinase CK2, providing an important molecular basis for the development of novel therapeutic drugs. This paper provides a systematic review of the chemical structure, sources, pharmacological activity, mechanism of action, druggability, and clinical application prospects of Chirenol, aiming to provide a reference for the fields of natural product pharmacology and new drug development.

Chemical structure and physicochemical properties

Chirenol (CAS No.: 52659-56-0) has the molecular formula C20H30O4 and a molecular weight of 338.4880. Its structure belongs to the diterpene compounds, featuring a typical terpene backbone, containing multiple hydroxyl groups and double bonds, which impart high biological activity. The LogP value of chirenol is 2.2332, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 80.92 Ų, indicating that it has certain polar groups that facilitate binding to biomacromolecules. It has low water solubility (0.2383 mg/mL), but good oral bioavailability and high blood-brain barrier permeability, making it suitable for research in the treatment of central nervous system diseases. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity; The Ames-induced mutagenic test result was 0.0, indicating a low genotoxicity risk.

Plant Origins and Extraction Methods

Chirenol is mainly found in various Chinese medicinal materials and traditional medicinal plants, with the roots, stems, and leaves of certain herbs being the most concentrated sites. Common source plants include certain legumes and labiaceae, which are widely used in traditional medicine for anti-inflammatory, analgesic, and bone health benefits. Extraction methods often use organic solvent reflux or ultrasound-assisted extraction, combined with silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) for separation and purification, enabling the acquisition of high-purity chirenol. In recent years, the application of supercritical CO₂ extraction and membrane separation technologies has improved extraction efficiency and purity, reduced solvent residues, and facilitated subsequent pharmacological research and formulation development.

Pharmacological activity research

Chirenol exhibits a wide range of pharmacological activities, covering anti-tumor, anti-inflammation, anti-fibrosis, antioxidant, neuroprotection, cardioprotection, renal protection, and pain relief.

Antitumor activity

Chirenol exerts antitumor effects by inducing cancer cell apoptosis and cell cycle arrest. Its mechanisms inducing apoptosis include promoting Bid lysis to tBid, regulating the expression and phosphorylation status of Bax, Bcl-2, p53, and p21 proteins, leading to loss of mitochondrial membrane potential and accumulation of reactive oxygen species (ROS). Additionally, the apoptosis induced by chirenol does not depend on the caspase pathway, suggesting it may exert anticancer effects via non-classical pathways. Cell cycle analysis showed that Chirenol can induce S phase blockade and inhibit cancer cell proliferation. Multiple tumor model studies have confirmed its potential inhibitory effect on malignant tumors such as chronic myeloid leukemia.

Anti-inflammatory and immunomodulatory

Chirenol significantly inhibits various inflammatory signaling pathways, including NF-κB, TGF-β/Smads, and NLRP3 inflammasomes, reduces the expression of pro-inflammatory factors such as IL-6 and TNF-α, and alleviates inflammatory responses. It regulates key inflammation-related targets such as CASP1, STAT3, TRPV1, TRPA1, NOS2, PTGS1, and PTGS2, demonstrating good anti-inflammatory activity. In animal models, Chirenol effectively alleviated acute lung injury, diabetic nephropathy, and heart failure-related inflammatory damage, demonstrating good immunomodulatory potential.

Antioxidant and cell protection

Chirenol promotes mitochondrial fusion and mitophagy, maintains mitochondrial function stability, reduces excessive ROS accumulation, and exerts antioxidant effects. It activates the AMPK-mTOR-ULK1 signaling pathway, inducing autophagy to help clear damaged organelles and protect cells from oxidative stress damage. In ischemic stroke models, chirenol significantly improves neurological deficits by reducing oxidative stress and inflammatory responses, demonstrating neuroprotective effects.

Regulation of bone metabolism

Chirenol promotes osteoblast differentiation, regulates BMP and Wnt/β-catenin signaling pathways, and facilitates bone formation and mineralization. It has shown good bone protection effects in osteoporosis models and has potential value in regulating bone metabolism.

Mechanism of action and molecular targets

The multi-target mechanism of chirenol is the basis for its remarkable pharmacological activity. Its main targets include the protein kinase CK2 (Kd=5.47 μM), which regulates the CK2/AKT signaling pathway, affecting cell proliferation, apoptosis, and metabolic balance. Additionally, Chirenol activates the AMPK-mTOR-ULK1 pathway, promoting autophagy and mitophagy to protect cellular function. It inhibits NF-κB, TGF-β/Smads, and NLRP3 inflammasome signaling, reducing inflammatory responses. Chirenol also regulates the GSK3β, BMP, and Wnt/β-catenin pathways, participating in cell differentiation and tissue repair.

In apoptosis regulation, Chirenol promotes Bid cleavage to tBid, modulates the Bax/Bcl-2 ratio, activates p53 and p21, and induces cell cycle arrest and non-caspase-dependent apoptosis. The accumulation of ROS further promotes cell death signaling. The synergistic effect of these multiple signaling pathways enables crerenol to demonstrate complex therapeutic potential in various pathological states.

Druggability evaluation and pharmacokinetics

The physicochemical properties of Chirenol meet the basic requirements for drug development. Its moderate molecular weight and lipophilic solubility ensure good cell membrane penetration and oral absorption. The high permeability of the blood-brain barrier makes it suitable for treating neurological diseases. Although low water solubility may affect bioavailability, it can be effectively improved through formulation optimization (such as nanocarriers, liposomes, etc.).

In terms of safety, Chirenol does not have significant hERG channel inhibitory effects and carries a low risk of cardiotoxicity. A negative Ames test indicates a low genotoxicity risk and is suitable for long-term use. Current pharmacokinetic studies show that Chirenol is widely distributed in the body, has stable metabolism, is mainly excreted by the liver, has a moderate half-life, and is suitable for clinical administration.

Prospects and outlooks for clinical applications

Based on the multi-target and multi-mechanism pharmacological properties of chirenol, it shows broad application prospects in the treatment of various diseases. In the antitumor field, Chirenol can be used as an adjunct or combination therapy to enhance chemotherapy efficacy and reduce drug resistance. Its anti-inflammatory and immunomodulatory effects give it potential value in autoimmune diseases, chronic inflammation, and acute injury. Neuroprotective and cardioprotective effects offer new approaches for treating diseases such as ischemic stroke and heart failure. The function of regulating bone metabolism offers potential for treating bone-related diseases such as osteoporosis.

Future research should further clarify the pharmacokinetic characteristics and safety evaluation of Chirenol, optimize the route of administration and formulation form, conduct preclinical and clinical trials, and verify its efficacy and safety. In addition, based on its multi-target mechanism of action combined with modern drug design technologies, developing cirrenol derivatives or combination therapy regimens will help enhance its clinical value.

Conclusion

As a natural diterpenoid compound with significant pharmacological activity, Chirenol demonstrates broad therapeutic potential with its multi-target regulatory capability and good druggability. Its research achievements in anti-tumor, anti-inflammation, antioxidant, and tissue protection have provided valuable resources for natural product pharmacology and new drug development. In the future, as mechanistic research deepens and clinical validation advances, Chirensol is expected to become a novel candidate for treating various major diseases, driving the transformation of natural products into clinical practice.