Synonym name: 3'-Hydroxy-3,4,4',5-tetramethoxybibenzyl
Catalogue No.: BP0550
Cas No.: 95041-90-0
Formula: C₁₈H₂₂O₅
Mol Weight: 318.369
Botanical Source: Eria carinata

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:

Erianin, often used as an antipyretic and analgesic agent, it also has antiangiogenic action by inhibiting endothelial metabolism in a JNK/SAPK-dependent manner and inducing endothelial cytoskeletal disorganisation.

References:

Invest New Drugs. 2012 Oct;30(5):1899-907.    

ZJU-6, a novel derivative of Erianin, shows potent anti-tubulin polymerisation and anti-angiogenic activities.   

ZJU-6 was designed to enhance anti-angiogenesis and anti-tumour activity of its parent compound Erianin, a clinic anti-tumour agent. This study investigated the detailed biological mechanism of ZJU-6 in comparison with that of Erianin. 

METHODS AND RESULTS:

Both ZJU-6 and Erianin substantially reduced cell viability and induced apoptosis in human cancer cell lines. Profound G2/M cell arrest was observed 24 h after treatment of MCF-7 cells with ZJU-6 (≥ 2.5 μM) or Erianin (≥ 0.1 μM); being consistent with mitotic collapse. 0.5 μM of Erianin or ZJU-6 failed to stabilise tubulin. Pre-G1 MCF-7 cell accumulating 24 h post treatment indicated apoptosis. Caspase-3 activity, PARP cleavage and Annexin V + ve /PI -ve populations correlate the apoptotic destiny of cells exposed to either ZJU-6 or Erianin. Furthermore ZJU-6 showed potent anti-angiogenetic property and demonstrated radical scavenging capacity. 

CONCLUSIONS:

Due to its potent anti-proliferative, pro-apoptotic and anti-angiogenic activities ZJU-6 is an attractive chemotherapeutic agent to be developed.    

Acta Pharmacol Sin. 2001 Nov;22(11):1018-22.    

Erianin induces apoptosis in human leukemia HL-60 cells.   

To investigate the effect of Erianin on human HL-60 cell line and explore its mechanism of apoptosis in vitro. 

METHODS AND RESULTS:

Inhibition of proliferation was measured with colorimetric MTT assay. The morphologic changes were observed by fluorescence and electron microscopes. DNA fragmentation was visualized by agarose gel electrophoresis, and the DNA degradation was determined by flow cytometry. Immunohistochemical analysis was used to identify the expression of bcl-2 and bax genes. The growth of human HL-60 cells was significantly inhibited by Erianin 20-81.9 nmol/L during 72 h treatment (P < 0.01). The IC50 value was 38 nmol/L after a 24-h exposure to Erianin, while that of vincristine, the positive control, was 101 nmol/L. The typical morphologic changes were observed and the nuclear DNA fragmentation exhibited "ladder" pattern. The cell cycle of HL-60 cells was arrested in G2/M phase, and expression of bcl-2 gene was decreased while that of bax was increased. 

CONCLUSIONS:

Erianin showed potent inhibitory activity on the proliferation of HL-60 cells. The inhibition might be relative to the apoptosis induced by Erianin and the altered expression of bcl-2 and bax genes in HL-60 cells.    

Eur J Cancer. 2004 Jul;40(10):1554-65.    

In vivo and in vitro evaluation of erianin, a novel anti-angiogenic agent.   

This study evaluated the anti-angiogenic activities of Erianin in vivo and in vitro. 

METHODS AND RESULTS:

Erianin, a natural product from Dendrobium chrysotoxum, caused moderate growth delay in xenografted human hepatoma Bel7402 and melanoma A375 and induced significant vascular shutdown within 4 h of administering 100 mg/kg of the drug. Erianin also displayed potent anti-angiogenic activities in vitro: it abrogated spontaneous or basic fibroblast growth factor-induced neovascularisation in chick embryo; it inhibited proliferation of human umbilical vein endothelial cells (EC(50) 34.1+/-12.7 nM), disrupted endothelial tube formation, and abolished migration across collagen and adhesion to fibronectin. Erianin also exerted selective inhibition toward endothelial cells, and quiescent endothelium showed more resistance than in proliferative and tumour conditions. In a cytoskeletal study, Erianin depolymerised both F-actin and beta-tubulin, more significantly in proliferating endothelial cells than in confluent cells. In conclusion, Erianin caused extensive tumour necrosis, growth delay and rapid vascular shutdown in hepatoma and melanoma models; it inhibited angiogenesis in vivo and in vitro and induced endothelial cytoskeletal disorganisation. 

CONCLUSIONS:

These findings suggest that Erianin has the therapeutic potential to inhibit angiogenesis in vivo and in vitro.    

HPLC of Erianin

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

Introduction/Overview

Natural products have long been an important treasure trove for innovative drug discovery, with many compounds receiving significant attention due to their unique chemical structures and broad biological activities. Erianin, also known as 2-methoxy-5- [2- (3,4,5-trimethoxyphenyl) ethyl] phenol, is a benzyl compound isolated from plants of the Dendrobium genus in the Orchidaceae family. Since its discovery, berberine has become a hot topic in natural product pharmacology research due to its significant anti-tumor, anti-inflammatory, analgesic, antipyretic and other multiple pharmacological activities. Of particular note is the strong anti angiogenic and direct anti-tumor effects exhibited by Maolansu in various tumor models. Its mechanism of action involves inducing cell apoptosis, autophagy, ferroptosis, and regulating multiple signaling pathways closely related to tumor occurrence and development. With the development of modern molecular biology and pharmacology techniques, the target network of berberine is becoming increasingly clear, laying a solid scientific foundation for its development as a lead compound. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of Ranunculin, in order to provide comprehensive references for the in-depth research and future drug development of this compound.

Chemical structure and physicochemical properties

Maolansu is a derivative of diphenylethane, specifically 1,2-dihydrostilbene substituted with hydroxyl at position 3 and methoxy at positions 4, 3 ', 4', and 5 '. Its molecular formula is C18H22O5 and its molecular weight is 318.3690. Structurally, Ranunculin belongs to the class of benzyl compounds, with its core structure consisting of two benzene rings connected by an ethane bridge. This structure endows it with a certain hydrophobicity, and its calculated LogP value is 3.3614, indicating that it has good lipid solubility. Its topological polar surface area (TPSA) is 57.15 Å ², which is relatively small due to the presence of only one phenolic hydroxyl group and four methoxy groups in its molecule.

In terms of physical and chemical properties, Maolansu has poor water solubility, with a calculated value of about 0.0394 mg/mL. This to some extent limits its direct development as an aqueous formulation, but also suggests that it may have good cell membrane penetration ability. Pharmacokinetic predictions indicate that berberine has a high potential to penetrate the blood-brain barrier, providing possibilities for its potential neuroprotective or therapeutic applications in central nervous system related diseases. The preliminary safety assessment shows that the hERG inhibition risk is negative, and the Ames test prediction result is negative (0.0), indicating a low potential risk of arrhythmia and genetic toxicity, providing favorable early safety features for its drug development.

Plant sources and extraction methods

Maolansu mainly comes from various plants of the Dendrobium genus in the Orchidaceae family, and is one of the characteristic active ingredients of these medicinal plants. Common sources include Dendrobium nobile, Dendrobium officinale, and Dendrobium huoshanense. Dendrobium plants are commonly used in traditional Chinese medicine to nourish yin, clear heat, benefit the stomach, and produce fluids. Modern research has gradually revealed the material basis of their anti-tumor, immune regulating, and other activities, with Ranunculin being one of the key components.

Organic solvent extraction is commonly used to extract berberine from plant materials. The common process includes crushing the dried stem of Dendrobium officinale, and using high concentration ethanol (such as 95% ethanol) or methanol for reflux extraction or ultrasound assisted extraction. The extract is concentrated under reduced pressure to obtain a paste, which is then extracted in stages using solvents of different polarities such as petroleum ether, ethyl acetate, and n-butanol. Maolansu is mainly enriched in the ethyl acetate extraction site. Subsequently, high-purity Ranunculin monomer can be obtained through separation and purification techniques such as silica gel column chromatography and preparative high-performance liquid chromatography, combined with thin-layer chromatography or high-performance liquid chromatography for tracking and detection. With the development of technology, green extraction methods such as supercritical fluid extraction have also been applied to improve extraction efficiency and reduce the use of organic solvents.

Pharmacological activity research

Maolansu exhibits broad and powerful pharmacological activities, making it a highly valuable lead compound for research.

1. Antitumor activity This is the most highly regarded activity of Ranunculin. Studies have shown that Maolansu can significantly inhibit the proliferation and induce death of many tumor cell lines, such as liver cancer, breast cancer, lung cancer, colon cancer, bladder cancer, ovarian cancer, osteosarcoma, etc. Its anti-tumor effect is not limited to directly killing tumor cells, but also manifested in inhibiting tumor angiogenesis, that is, exerting its effect by "starving" the tumor.
2. Anti angiogenic activity Maolansu has been proven to be an effective angiogenesis inhibitor. It can specifically inhibit tumor angiogenesis induced by indoleamine-2,3-dioxygenase (IDO), disrupt the tumor's blood supply network, and thus inhibit tumor growth and metastasis.
3. Anti inflammatory and immune regulatory activity Maolansu can inhibit the inflammatory response induced by stimuli such as lipopolysaccharides and reduce the expression of pro-inflammatory cytokines (such as TNF - α, IL-6, IL-1 β). Its anti psoriasis activity is also closely related to inhibiting excessive proliferation of keratinocytes and reducing skin inflammation.
4. Analgesic and antipyretic activity As a non anesthetic analgesic and antipyretic, berberine exerts central analgesic and antipyretic effects through mechanisms different from opioid drugs, without addictive risks, and has good application prospects.
5. Neuroprotective activity Maolansu has a protective effect on nerve cells and may exert beneficial effects in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease through mechanisms such as antioxidant and anti apoptotic effects.
6. Antibacterial and antioxidant activity Research has shown that berberine has inhibitory effects on certain bacteria and fungi. Meanwhile, its phenolic hydroxyl structure endows it with certain abilities to scavenge free radicals and resist oxidation.
7. Inducing programmed cell death Maolansu can induce apoptosis, autophagy, and ferroptosis in tumor cells simultaneously or under different conditions, and this multi-mode cell death induction ability is the key to its potent anti-tumor effect.

Mechanism of action and molecular targets

The various pharmacological activities of berberine, especially its core anti-tumor effect, are achieved by intervening in complex intracellular signaling networks. Taking liver cancer as an example, its effects involve multiple key targets and pathways:

1. Inducing cell apoptosis Maolansu can upregulate pro apoptotic proteins (such as Bax) and downregulate anti apoptotic proteins BCL2 Thereby inducing cell apoptosis through the mitochondrial pathway. Meanwhile, it can inhibit STAT3 The activation of signaling pathways, and STAT3 is a key transcription factor that promotes cell survival, proliferation, and immune escape.
2. Inhibition of cell proliferation and DNA damage Maolansu can directly act on Topoisomerase I (TOP1)Interference with DNA replication and transcription, leading to DNA damage and cell cycle arrest.
3. Inhibit tumor angiogenesis Maolansu can downregulate hypoxia inducible factor HIF1A Expression and inhibition of matrix metalloproteinases MMP9 The activity of the tumor disrupts the microenvironment for tumor angiogenesis, invasion, and metastasis. Its inhibition of IDO induced angiogenesis is also related to regulating the immune microenvironment.
4. Regulating inflammation and survival signaling pathways Maolansu can inhibit key kinases in the nuclear factor kappa B (NF - κ B) pathway IKBKB To prevent its inhibition of subunit I κ B phosphorylation degradation, thereby inhibiting transcription factors RELA（p65） The nuclear translocation ultimately reduces the expression of a series of pro-inflammatory and pro survival genes. It can also inhibit PI3K/Akt Pathway (target)PIK3CA）And MAPK/ERK Pathway (target)MAPK1）These two pathways are crucial in cell growth, metabolism, and survival.
5. Inducing autophagy and ferroptosis Maolansu can induce protective or lethal autophagy by activating pathways such as AMPK. In addition, it can induce iron dependent cell death through mechanisms such as consuming glutathione and promoting lipid peroxidation.
6. Telomerase inhibition Maolansu has been reported to inhibit telomerase reverse transcriptase TERT The activity may affect the unlimited proliferation potential of tumor cells.

In summary, Maolansu forms a powerful anti-tumor network through multi-target and multi pathway synergistic effects, which is also one of its potential advantages in not easily developing drug resistance.

Evaluation of drug properties and pharmacokinetics

Although Maolansu has shown excellent activity in vitro and preclinical models, its pharmacological properties still need to be comprehensively evaluated.

1. Absorption, distribution, metabolism, excretion Currently, research on the pharmacokinetics of the berberine system is relatively limited. Based on its physicochemical properties (moderate LogP value, small TPSA), it is predicted that its oral absorption may be acceptable, but the absolute bioavailability needs to be confirmed through experiments. Its high blood-brain barrier permeability prediction provides the possibility for its treatment of brain diseases or brain metastases. As a phenolic compound, berberine is likely to undergo extensive phase II metabolism in the body, such as glucuronidation and sulfation, and may also be metabolized by the cytochrome P450 enzyme system. Further in vivo studies are needed to clarify key parameters such as metabolites, excretion pathways (bile or urine), and half-life.
2. Formulation and delivery strategy Due to its poor water solubility, developing suitable drug delivery formulations is key to promoting its clinical application. Nanotechnology provides a solution for this, and nanocarrier systems such as liposomes, polymer nanoparticles, micelles, etc. have been used to encapsulate berberine, aiming to improve its solubility, stability, tumor targeting, and bioavailability while reducing systemic toxicity.
3. safety evaluation The existing computational predictions (hERG negative, Ames negative) provide preliminary optimistic signals. However, comprehensive preclinical safety evaluation, including studies on acute toxicity, long-term toxicity, reproductive toxicity, carcinogenicity, etc., is crucial. Some studies have reported the effective dose and tolerable range of berberine in animal models, but more systematic toxicological data still needs to be improved.

Clinical application prospects and prospects

Maolansu has moved from laboratory research to clinical application, with broad prospects but challenges.

1. Antitumor therapy This is the most promising direction for Maolansu. It may be used as a single drug or in combination with existing chemotherapy, targeted therapy and immunotherapy drugs to treat liver cancer, bladder cancer, osteosarcoma and other malignant tumors. Its anti angiogenic and immune regulatory properties make it uniquely valuable in reshaping the tumor microenvironment. Targeted formulations based on nanotechnology are expected to deliver them specifically to tumor sites, achieving increased efficacy and reduced toxicity.
2. Inflammatory and autoimmune diseases Its strong anti-inflammatory activity makes it of exploratory value in the treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and other diseases.
3. Pain and fever management As a non addictive analgesic and antipyretic drug, berberine may provide a new option for chronic pain or postoperative pain management.
4. Neurodegenerative diseases Its neuroprotective effect provides new candidate molecules for drug development in Alzheimer's disease and Parkinson's disease.

The challenges faced mainly include:① Insufficient pharmacokinetic and toxicological data in the system；② Poor water solubility requires the development of an efficient delivery system；③ The target network is complex, and it is necessary to clarify the core targets and potential off target effects that exert therapeutic effects；④ Need to design and complete standardized preclinical studies and clinical trials To confirm its safety and effectiveness.

Future research directions should focus on: delving into the precise molecular mechanisms underlying its multi-target effects; Using structural biology and computer-aided drug design to optimize its structure and improve its drug properties; Accelerate the development of new nano or prodrug formulations; Conduct systematic preclinical safety and efficacy evaluations, and actively promote eligible candidate drugs to enter the clinical research stage.

Conclusion

Maolansu, as a natural benzyl compound derived from traditional medicinal plants, has become a star in the field of natural product anti-tumor drug research due to its diverse pharmacological activities and unique multi-target mechanism of action. From chemical structure to plant origin, from basic pharmacology to complex action networks, research has preliminarily outlined the clear outline of Ranunculin as an efficient and multifunctional lead compound. Its outstanding ability to induce multiple programmed cell deaths, inhibit tumor angiogenesis, and regulate immune inflammatory responses provides new strategies and hope for its treatment in major diseases such as tumors and inflammation. Although there are still many challenges in drug formulation, delivery technology, and clinical translation, these obstacles are gradually being overcome with the rapid development of modern pharmaceutical technology. Through interdisciplinary and continuous in-depth research and development, it is highly likely that Maolansu will move from the laboratory to clinical practice, ultimately benefiting human health and fully demonstrating the immortal value and vitality of natural products in innovative drug development.