Product name: Cimiracemoside D
Synonym name: 12-beta-acetoxycimigenol-3-O-alpha-L-arabinopyranside
Catalogue No.: BP1565
Cas No.: 290821-39-5
Formula: C₃₇H₅₈O₁₁
Mol Weight: 678.86
Botanical Source: Constit. of Cimicifuga racemosa
Physical Description: Powder
Type of Compound: Triterpenoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

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

HPLC of Cimiracemoside D

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

Introduction/Overview

Natural products have always been an important source of innovative drug discovery, and their structural diversity and biological activity provide unique molecular frameworks and lead compounds for the treatment of various complex diseases. Black cohosh（Cimicifuga racemosa As a traditional medicinal plant, it has long been used in North America and Asia to treat menopausal syndrome, rheumatic pain, and inflammatory diseases in women. Modern pharmacological studies reveal that its active ingredients are complex and diverse, mainly including triterpene saponins, phenolic acids and other components, among which cyclo jackfruit alkyl triterpene saponins are considered as the key material basis for its multiple pharmacological effects.

Cimiracemoside D (CAS No. 290821-39-5) is a cyclic jackfruit alkyl triterpene saponin isolated from black cohosh in recent years. Although the specific background of its activity is not yet clear in early research, based on its parent nucleus structural analogues (such as coumarin compounds), it has been reported to have anti-inflammatory, anti osteoporosis, neuroprotective, and potential anti-tumor activities, which has attracted the attention of researchers. It is particularly worth exploring in depth that preliminary bioinformatics and target prediction analysis suggest that Cimiracemoside D may interact with multiple key targets closely related to tumor occurrence and development, such as apoptosis regulatory proteins (MCL1, BCL2), signal transduction and transcriptional activation factors (STAT3), matrix metalloproteinases (MMP2), and topoisomerases (TOP1, TOP2A). This provides important theoretical clues for its potential application value in the field of anti-tumor.

This article aims to provide a systematic review of Cimiracemoside D, including its chemical structure, plant origin and extraction, pharmacological activity, mechanism of action, drug evaluation, and clinical application prospects, in order to provide comprehensive scientific references for the in-depth research and development of this natural product.

Chemical structure and physicochemical properties

Acetylcohoshenol-3-arabinoside is a cyclic jackfruit alkyl triterpene saponin. Its molecular formula is C ∝₅ H ₅₈ O ₁₂, and its molecular weight is 678.8600. Its basic structural skeleton is a cyclic jackfruit alkane triterpene with four rings, and a arabinose group is connected to the C-3 hydroxyl group to form a glycosidic bond. The characteristic of this compound is the presence of acetylation modification on its sugar moiety or glycoside backbone ("Acetyl Cimicinolol" suggests the presence of acetyl groups), which may significantly affect its lipid solubility, cell membrane permeability, and interaction mode with target proteins.

According to the provided pharmacological parameters, its lipid water partition coefficient (LogP) is 2.8930, indicating that the compound has moderate lipophilicity, which theoretically facilitates its penetration into cell membranes. Its topological polar surface area (TPSA) is 164.3700 Å ², which is relatively high. This is mainly attributed to the presence of multiple hydroxyl groups and oxygen atoms on the sugar ring in the molecule, which are potential hydrogen bond donors and acceptors. Higher TPSA typically affects the membrane permeability of compounds. Its water solubility parameter is 0.0117 mg/mL, belonging to the category of slightly soluble or poorly soluble in water, which is consistent with the properties of most triterpenoid saponins. Solubilization strategies may need to be considered in formulation development.

In addition, the prediction shows that its ability to cross the blood-brain barrier is relatively low, which suggests that it may not be suitable for the treatment of primary central nervous system tumors, but it may also mean that peripheral side effects are relatively small. HERG inhibition prediction is negative, indicating a low potential risk of cardiac toxicity, which is a favorable pharmacological feature. The Ames test predicted a value of 0.0, indicating that it may not be mutagenic, but further experimental verification is needed.

Plant sources and extraction methods

Cimiracemoside D is mainly derived from the black cohosh plant in the Ranunculaceae family（Cimicifuga racemosa The rhizome of (L.) Nutt. Black cohosh is mainly distributed in the eastern part of North America, and its dry rhizome is a traditional medicinal part. Apart from black cohosh, other plants belonging to the same genus such as Xing'an cohosh（C. dahurica）Da San Ye Sheng Ma（C. heracleifolia）It may also contain saponin components with similar structures, but the specific composition spectrum varies among species.

The extraction and separation of Cimiracemoside D from plant materials typically follow the conventional process of natural product chemistry:
1. Extract Usually, methanol, ethanol, or ethanol water mixed solvents are used for reflux extraction or ultrasound assisted extraction of dried and crushed black cohosphae rhizomes to maximize the extraction of triterpenoid saponins with a wide range of polarities.
2. Rough classification The extract obtained by vacuum concentration of the extract is often subjected to gradient extraction using organic solvents such as petroleum ether, ethyl acetate, n-butanol, etc. Cimiracemoside D is usually enriched in the highly polar n-butanol extraction site due to its glycosidic structure.
3. Separation and Purification The n-butanol fraction is further separated and purified using various chromatographic techniques. Silica gel column chromatography is commonly used for preliminary separation, with gradient elution using chloroform methanol or dichloromethane methanol systems in different ratios. Then, the target stream was repeatedly purified until the monomer compound was obtained by combining reverse phase silica gel column chromatography (such as C18 packing, methanol water or acetonitrile water as mobile phase), dextran gel column chromatography (such as Sephadex LH-20) and high performance liquid chromatography (HPLC, especially preparative HPLC). Structural identification involves the comprehensive use of spectroscopic techniques such as nuclear magnetic resonance (NMR, including ¹ H, ¹ ³ C, 2D-NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

At present, there are few reports on the optimization of the extraction process and large-scale preparation of Cimiracemoside D. If its pharmacological activity is confirmed in the future, the development of efficient and environmentally friendly extraction and separation processes will be the key to its sustainable resource utilization.

Pharmacological activity research

Although the direct pharmacological activity experimental data of Cimiracemoside D is not yet abundant in public literature, based on its structural category (black cohosphaceae triterpenoid saponins) and preliminary target prediction information, the core pharmacological activity research focus is on antitumor field The prediction of relevant targets strongly suggests their potential intervention ability in various tumor related pathways and processes.

1. Inducing apoptosis of tumor cells The predicted targets MCL1 and BCL2 are important anti apoptotic proteins in the Bcl-2 family, which are overexpressed in various cancers and help tumor cells evade programmed cell death. STAT3 is a key oncogenic transcription factor that continuously activates to promote cell proliferation, survival, and inhibit apoptosis. Cimiracemoside D may restore the apoptotic sensitivity of tumor cells by inhibiting these targets.
2. Inhibit tumor invasion and metastasis Matrix metalloproteinase MMP2 can degrade extracellular matrix and plays a central role in tumor invasion and metastasis. Inhibiting MMP2 activity is an important strategy for anti-tumor metastasis.
3. Interference with DNA replication and repair Topoisomerase TOP1 and TOP2A are essential enzymes for DNA replication, transcription, and chromosome separation, and are targets of various classic chemotherapy drugs such as irinotecan and etoposide. Cimiracemoside D may cause DNA damage and cell death by inhibiting the activity of these enzymes.
4. Affects tumor microenvironment and hormone regulation The target HIF1A is a core regulatory factor for cellular response to hypoxia, closely related to tumor angiogenesis, metabolic reprogramming, and chemoradiotherapy resistance. MAPK1 (ERK2) is a key kinase in the MAPK/ERK signaling pathway, regulating cell growth and differentiation. ESR1 (estrogen receptor α) and CYP19A1 (aromatase) are closely related to the occurrence and development of hormone dependent tumors (such as breast cancer). Black cohosh extract has traditionally been used to alleviate menopausal symptoms, with some mechanisms related to estrogen receptor regulation. Therefore, Cimiracemoside D may also play a role in this regard.

In addition to anti-tumor effects, the anti-inflammatory, antioxidant, neuroprotective, and anti osteoporosis activities of the extract of total saponins from black cohosphae have been widely studied, which may also be partially attributed to the contribution of monomeric components such as Cimiracetamide D, but this needs to be directly verified by subsequent experiments.

Mechanism of action and molecular targets

Based on existing target predictions, Cimiracemoside D may exert anti-tumor effects through synergistic effects of multiple targets and pathways. The potential mechanism network can be preliminarily outlined as follows:

• Activate mitochondrial apoptosis pathway By directly or indirectly inhibiting the functions of anti apoptotic proteins MCL1 and BCL2, it may lead to increased mitochondrial outer membrane permeability, release of cytochrome C, activation of caspase cascade reaction, and ultimately induce tumor cell apoptosis.
• Blocking carcinogenic signal transduction Inhibiting the phosphorylation or dimerization of STAT3 can downregulate the expression of downstream target genes such as Bcl xL, Cyclin D1, VEGF, thereby inhibiting cell proliferation, survival, and angiogenesis. Meanwhile, potential inhibition of MAPK1 (ERK2) may interfere with growth factor signaling and block cell cycle progression.
• Inhibition of enzyme activity and DNA damage As a potential inhibitor of topoisomerase TOP1/TOP2A, Cimiracemoside D may stabilize the enzyme DNA cleavage complex, prevent DNA reconnection, cause DNA double strand breaks, trigger DNA damage responses, and lead to cell death.
• Anti invasion and anti angiogenesis By inhibiting the activity or expression of MMP2, the ability of tumor cells to degrade the basement membrane and extracellular matrix is reduced, thereby inhibiting their invasion and metastasis. Meanwhile, by interfering with the stability or transcriptional activity of HIF1A, it is possible to downregulate the expression of angiogenic factors such as VEGF and inhibit tumor angiogenesis.
• Regulating hormone related pathways For estrogen receptor positive tumors, Cimiracemoside D may act as a regulator of ESR1 (agonist or antagonist to be determined experimentally), or reduce estrogen levels in the body by inhibiting CYP19A1 (aromatase), thereby inhibiting hormone dependent tumor cell growth.

It should be emphasized that the above mechanism network is mainly based on bioinformatics prediction and analogy speculation of similar compounds. The exact mechanism of action of Cimiracemoside D, including whether it directly binds to these targets, its binding affinity, and how it affects downstream signaling networks, needs to be further validated and elucidated through modern molecular pharmacology techniques such as molecular docking, surface plasmon resonance (SPR), enzyme activity inhibition experiments, reporter gene detection, gene knockout/overexpression, and proteomics.

Evaluation of drug properties and pharmacokinetics

Based on the provided calculated chemical parameters, a preliminary analysis is conducted on the pharmacological properties of Cimiracemoside D

• Absorption and permeability The molecular weight of 678.86 is slightly higher than the "500 Dalton rule" commonly believed to be easily absorbed orally. A moderate LogP value (2.89) is favorable for passive diffusion, but higher TPSA (164.37 Å ²) and glycoside structure may limit its transmembrane permeability, especially intestinal absorption. Its low water solubility (0.0117 mg/mL) is a major challenge for oral bioavailability, which may result in limited dissolution rate and absorption.
• distribution It is predicted that its blood-brain barrier permeability is low, mainly due to its higher polar surface area and molecular weight. This means that it may be mainly distributed in peripheral tissues and organs, which may be an advantage for treating peripheral solid tumors, but not conducive to treating brain tumors.
• Metabolism and excretion As a glycoside compound, Cimiracemoside D may face two main metabolic pathways in vivo: one is that the glycosidic bond is hydrolyzed by glycosidases in the gut microbiota or tissues, producing aglycones (acetylcannabinol) and arabinose, and the activity and pharmacokinetic behavior of aglycones may be different from the original drug; The second is the occurrence of phase I (such as oxidation and reduction) and phase II (such as glucuronidation and sulfation) metabolic reactions. Currently, there is a lack of specific data on the interactions between metabolic enzymes, such as CYP450 isoenzymes.
• Preliminary Safety Prediction The negative prediction of hERG inhibition reduces its risk of causing QT interval prolongation in the heart, which is a positive signal. The negative prediction of Ames test suggests that its genetic toxicity risk may be low. However, the safety of natural products needs to be comprehensively evaluated, including acute and chronic toxicity, organ toxicity (especially the potential hemolytic and gastrointestinal irritation of triterpenoid saponins), and interactions with other drugs.

Overall, Cimiracemoside D exhibits certain potential for drug development (such as moderate lipid solubility and no hERG inhibition warning), but also faces common challenges from natural product drugs, such as poor solubility, potential poor oral absorption, and metabolic instability. Future pharmacokinetic research needs to focus on its absolute bioavailability, identification of metabolites in vivo, major excretion pathways, and tissue distribution characteristics.

Clinical application prospects and prospects

The clinical application prospects of Cimiracemoside D mainly depend on the depth of experimental verification of its anti-tumor activity and subsequent translational research progress.

1. As a candidate anti-tumor drug If in vitro and in vivo experiments can confirm its significant inhibitory activity against various tumor cells, especially those with apoptosis resistance, high metastasis, or hormone dependence, and its toxicity is controllable, it is expected to be developed into a novel anti-tumor drug. Its multi-target action characteristics may help overcome the resistance problem of single target drugs. It can be considered to explore the treatment of breast cancer, liver cancer, colorectal cancer and other malignant tumors closely related to STAT3, BCL2 family, MMPs and other targets.
2. Combination therapy strategy Given its potential to act on apoptosis pathways and DNA damage responses, the combination of Cimiracemoside D with existing chemotherapy drugs (such as topoisomerase inhibitors, platinum based drugs) or targeted drugs may result in synergistic effects, reducing the dosage of each drug, minimizing toxic side effects, and delaying the development of drug resistance.
3. Structural optimization and derivative development Reasonable structural modifications can be made to address the shortcomings of its medicinal properties, such as low water solubility and fast metabolism. For example, modifying the sugar moiety, derivatizing the glycoside backbone, or preparing prodrugs, phospholipid complexes, nano formulations, etc. to improve their solubility, stability, and bioavailability. By studying the structure-activity relationship, it is also possible to obtain derivatives with stronger activity and higher selectivity.
4. Expand other indications Based on the traditional use of black cohosh, the potential of Cimiracemoside D in treating menopausal syndrome related hot flashes, osteoporosis, and inflammatory diseases is also worth exploring, especially if its ESR1 regulatory activity is confirmed.

However, there are still many challenges in its clinical application: a large number of preclinical studies are needed to verify its effectiveness and safety; The problem of limited natural sources needs to be addressed, and sustainable supply may be achieved through plant cell culture, synthetic biology, or total chemical synthesis; A deep understanding of its complex mechanism of action network is needed to clarify its optimal indications and potential biomarkers.

Conclusion

As a cyclic jackfruit alkyl triterpenoid saponin isolated from the traditional medicinal plant Cimicifuga nigricana, acetyl cohosheol-3-arabinoside D has become a natural product molecule with considerable research value due to its unique chemical structure and preliminarily predicted association with multiple key tumor targets. Although direct biological experimental data is currently scarce, its multi-target intervention potential in inducing apoptosis, inhibiting metastasis, interfering with DNA metabolism, and regulating signaling pathways has drawn an exciting blueprint for its application in the field of anti-tumor drug development.

The current research is still in its early stages, and the focus of future work should be on: using modern pharmacological models and techniques to systematically validate its anti-tumor and other pharmacological activities at the cellular and animal levels; Comprehensively utilizing molecular biology, structural biology, and computational chemistry methods to elucidate its precise molecular mechanism of action and direct target of action; Systematically evaluate its pharmacokinetic characteristics and safety, and conduct rational formulation design and structural optimization research for its drug defects. Through interdisciplinary and in-depth research, Cimiracemoside D is expected to gradually develop from a potential natural lead compound into an important component of new drugs or drug combinations that can be used for clinical treatment, contributing its natural value to human health.