Product name: Aloe emodin
Synonym name: Rhabarberone
Catalogue No.: BP0146
Cas No.: 481-72-1
Formula: C₁₅H₁₀O₅
Mol Weight: 270.24
Botanical Source: Found in aloes, also bark of cascara sagrada, in Cassia alata, Rhamnus purshiana, Rhamnus alaternus, Rheum palmatum, Rheum undulatum, Rumex orientalis, Asphodelus microcarpus, Asphodelus fistulosus, Xanthorrhoea australis and Oroxylum indicum
Physical Description: Powder
Type of Compound: Anthraquinones

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams, up to kilograms
Inquire for bulk scale.

Descriptions:
Aloeemodin is able to interact with DNA under certain in vitro conditions, however, in vivo it is negative did not indicate a genotoxic potential, thus, it may be assumed that a genotoxic risk for man might be unlikely.[1]
Aloeemodin has inhibition of β-amyloid aggregation, and has neuroprotective effect on primary hippocampal cells against β-amyloid induced toxicity.[2]
Aloeemodin has anti-fibrotic effects, perhaps through downregulation of the expression of Smad2 mRNA and TGF-β1,TIMP1,and type Ⅰ and Ⅲ collagen proteins,and upregulation of the expression of Smad7 mRNA.[3]
Aloeemodin might have therapeutic effects on liver fibrosis induced by Schistosoma of liver through the effects of TGF-β1,VEGF and FAK expression.[4]
Aloeemodin can suppress the proliferation of HGC-27 cell to induce apoptosis and block cell cycle.[5]

References:
[1] Heidemann A, V?lkner W, Mengs U. Mutation Research/fundamental & Molecular Mechanisms of Mutagenesis, 1996, 367(3):123-33.
[2] Ho S L, Poon C Y, Lin C, et al. Current Alzheimer Research, 2015, 12(5):424-33.
[3] Wu Y Y, He S S. World Chinese Journal of Digestology, 2009, 17(27):2778-83.
[4] Dan X U, Zhou W, Hong-Gang Y U. Chinese Journal of Integrated Traditional & Western Medicine on Liver Diseases, 2012, 22(02):107-9.
[5] Nan J, Qin Y X, Liu J, et al. J Modern Oncol, 2008, 16(06):919-21.
[6]Chen C S, Sang X F. Chinese Journal of Health Laboratory Technology, 2011(05):1088-9.

HPLC of Aloe emodin

HNMR of Aloe emodin

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

Introduction/Overview

Natural products, as an important treasure trove for drug discovery and development, play an irreplaceable role in the long history of human fight against diseases. Among them, anthraquinone compounds have attracted much attention due to their wide range of biological activities. Aloe emodin (AE), chemical name 1,8-dihydroxy-3- (hydroxymethyl) anthraquinone, CAS number 481-72-1, is a typical natural product of dihydroxyanthraquinone. It was originally isolated from the traditional medicinal plant Aloe vera L. and is also widely present in various Polygonaceae and leguminous plants such as rhubarb and cassia seed. In history, plants containing aloe vera emodin were often used for diarrhea, heat clearing, and detoxification. With the deepening of modern pharmacological research, its role has shifted from traditional laxative components to lead compounds with significant anti-tumor, antiviral, anti-inflammatory, and antibacterial activities, especially showing great potential in the field of anti-tumor. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of aloe emodin, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The molecular formula of aloe emodin is C15H10O5, with a molecular weight of 270.24 g/mol. Its basic skeleton is anthraquinone (9,10-anthraquinone), with two phenolic hydroxyl groups at positions 1 and 8, and one hydroxymethyl group (- CH2OH) at position 3. This structure makes it a derivative of hydroxyanthraquinone, closely related in function to 1,8-dihydroxyanthraquinone (Chrysazine).

Its physicochemical properties profoundly affect its biological activity and pharmacokinetic behavior. Aloe emodin appears as orange yellow needle shaped crystals or powder. Its lipid water partition coefficient (LogP) is about 2.01, indicating that it has moderate lipophilicity and is conducive to transmembrane transport. The topological polar surface area (TPSA) is 94.83 Å ², reflecting the presence of polar groups (hydroxyl and carbonyl) in the molecule. Its water solubility is poor, about 0.1676 mg/mL, which to some extent limits its bioavailability. This compound is relatively stable at room temperature, but its phenolic hydroxyl structure gives it a certain antioxidant capacity and may also serve as a site for metabolic modification. The spectral characteristics are obvious, with characteristic absorption in the UV visible region and darkening color in alkaline solutions. These properties are commonly used for qualitative and quantitative analysis.

Plant sources and extraction methods

Aloe emodin is not unique to plants of the reed genus, but is widely distributed in various plants.
1. Main plant sources：
* Aloe genus Aloe vera, such as Aloe vera and Aloe ferox, mainly exist in the latex layer of the leaf skin.
* Rhubarb genus Rheum palmatum and Rheum tanguticum are among the main active ingredients of traditional Chinese medicine rhubarb.
* Jueming genus Such as Cassia obtusifolia and Cassia occidentalis.
* Rhamnus genus Such as Rhamnus fragula and other medicinal plants.
In these plants, aloe emodin often exists in the form of free aglycones or anthraquinone glycosides synthesized with sugars.

1. Extraction and Separation Methods：
   The extraction method is usually based on its polarity and solubility.
   • Solvent extraction method The most commonly used. Reflux or ultrasonic extraction is performed using methanol, ethanol, acetone, or alcohol water mixed solvents in different ratios. For aglycones, acid hydrolysis is often performed first to break glycosidic bonds, followed by extraction with organic solvents such as chloroform and ethyl acetate.
   • Modern extraction techniques Technologies such as supercritical fluid extraction (SFE, commonly CO2), microwave-assisted extraction (MAE), and ultrasound assisted extraction (UAE) have been applied due to their high efficiency and low solvent usage.
   • Separation and purification After stepwise solvent extraction, crude extracts are often separated and purified using methods such as silica gel column chromatography, polyamide column chromatography, preparative thin layer chromatography (PTLC), and high performance liquid chromatography (HPLC). Reverse phase HPLC is the standard method for obtaining high-purity aloe emodin.

Pharmacological activity research

Numerous in vitro and in vivo studies have confirmed that aloe emodin has diverse pharmacological activities.

1. Antitumor activity This is the most popular activity of aloe emodin. It exhibits significant growth inhibition and pro apoptotic effects on various human tumor cell lines, including but not limited to:

   • Hematological system tumors Such as Burkitt's lymphoma, leukemia, and multiple myeloma.
   • solid tumor: such as liver cancer, lung cancer, stomach cancer, colorectal cancer, breast cancer, cervical cancer, glioma, etc.
     Its anti-tumor effect is concentration - and time-dependent, and its toxicity to certain normal cells is relatively low, indicating that it has a certain degree of selectivity.

2. Antiviral activity Research has shown that aloe emodin has an inhibitory effect on influenza A virus, possibly by interfering with a certain link in the virus replication cycle. In addition, there have been preliminary research reports on its resistance to herpes simplex virus (HSV), human immunodeficiency virus (HIV), and other viruses.

3. Antibacterial and anti-inflammatory activity Aloe emodin has inhibitory effects on various Gram positive bacteria (such as Staphylococcus aureus, Bacillus subtilis) and some Gram negative bacteria. Its anti-inflammatory effect is related to the inhibition of pro-inflammatory factors (such as TNF - α, IL-6) production and inflammatory signaling pathways.

4. Other activities It also includes potential activities such as antioxidant, immune regulation, liver protection, and anti fibrosis. Its traditional laxative effect is mainly attributed to its stimulation of colonic peristalsis and impact on intestinal water and electrolyte balance.

Mechanism of action and molecular targets

The pharmacological effects of aloe emodin, especially its anti-tumor effect, are achieved through multi-target and multi pathway synergy.

1. Inducing cell cycle arrest Aloe emodin can block tumor cells at different stages of the cell cycle, such as G0/G1 phase or G2/M phase, which is usually associated with regulating the expression of cyclins, cyclin dependent kinases (CDKs), and CDK inhibitory proteins (such as p21, p27).

2. Inducing cell apoptosis This is one of the core mechanisms of its anti-tumor effect.

   • Mitochondrial pathway (endogenous pathway)Aloe emodin can reduce mitochondrial membrane potential, promote cytochrome C release, and activate the cascade reaction of caspase-9 and caspase-3. This process often involves regulating the balance of Bcl-2 family proteins, such as downregulating anti apoptotic proteins Bcl-2 and Bcl xL (BCL2L1), and upregulating pro apoptotic proteins Bax and Bak.
   • Death receptor pathway (exogenous pathway)Possible activation of caspase-8 may be achieved by upregulating the expression of death receptors such as Fas/FasL.
   • Endoplasmic reticulum stress pathway Inducing the expression of endoplasmic reticulum stress-related proteins such as CHOP and GRP78.

3. Inhibit cell invasion and metastasis By downregulating matrix metalloproteinases (MMPs, such as MMP-2 and MMP-9), inhibiting epithelial mesenchymal transition (EMT) process, and regulating related signaling pathways (such as Wnt/β - catenin), the migration and invasion of tumor cells are inhibited.

4. Inhibit angiogenesis Inhibiting tumor angiogenesis by reducing the expression of vascular endothelial growth factor (VEGF).

5. Regulating key signaling pathways and targets：

   • MTOR signaling pathway Recent studies have revealed that aloe emodin can directly bind to mTORC2 complex, inhibit its kinase activity, and thereby affect downstream signaling molecules such as Akt, which is crucial in regulating cell growth, metabolism, and survival.
   • PI3K/Akt pathway Aloe emodin is often reported to inhibit this pro survival pathway.
   • MAPK pathway It has different regulatory effects on the JNK, p38 MAPK, and ERK pathways, and the specific effects may vary depending on the cell type.
   • NF - κ B pathway Inhibiting the nuclear translocation and transcriptional activity of NF - κ B, thereby downregulating genes related to proliferation, apoptosis resistance, and inflammation that it regulates.
   • Specific molecular targets For example, inhibiting the activity of epidermal growth factor receptor (EGFR), regulating estrogen receptors (ESR1, ESR2), and affecting lipoxygenase (such as ALOX15). In disease models such as Burkitt's lymphoma, interventions targeting these targets may be the molecular basis for their therapeutic effects.

6. Autophagy regulation Aloe emodin can induce protective autophagy in some cases, while in others it may inhibit autophagy, and its role is context dependent.

Evaluation of drug properties and pharmacokinetics

Although aloe emodin has a wide range of activities, its medicinal properties still face challenges, with pharmacokinetic properties being its main bottleneck.

1. Absorption, distribution, metabolism, excretion (ADME)：

   • absorb After oral administration, aloe emodin has poor and irregular absorption in the intestine, with low bioavailability. This is mainly attributed to its low water solubility and possible intestinal metabolism/efflux.
   • distribution Due to its equal LogP value and low blood-brain barrier permeability, it is mainly distributed in tissues with abundant blood flow, such as the liver and kidneys, but difficult to enter the central nervous system.
   • Metabolism The liver is the main metabolic organ. The metabolic pathways include glucuronidation and sulfation of hydroxyl groups (II combined reaction), as well as possible reduction reactions (reduced by gut microbiota or tissues to anthrone products). The CYP450 enzyme system may be involved in its oxidative metabolism.
   • excretion Metabolites are mainly excreted through bile and urine.

2. safety evaluation：

   • Genotoxicity The Ames test result (value of 1.5) is generally considered to be within the critical range, indicating a slight mutagenic risk under specific conditions, but the data is not sufficient and needs to be comprehensively evaluated in conjunction with other genotoxicity tests. Some studies suggest that high concentrations of aloe vera emodin may cause DNA damage.
   • cardiotoxicity At present, data shows that it has no significant inhibitory effect on hERG potassium channels, indicating a low risk of causing long QT syndrome and cardiac toxicity.
   • Other toxicities Long term or high-dose use of anthraquinone containing plant medicines may cause colonic melanosis and potentially increase the risk of colon cancer. Aloe emodin may also have some toxicity to the kidneys.

3. Optimization strategy for drug properties：

   • Structural modification By synthesizing derivatives, such as preparing prodrugs, introducing solubilizing or active groups, to improve solubility, enhance activity, or reduce toxicity.
   • New drug delivery system Using nanotechnology, such as liposomes, nanoparticles, micelles, solid dispersions, etc., to encapsulate aloe emodin can significantly improve its solubility, stability, targeting, and bioavailability, and may reduce systemic toxicity.
   • combination therapy Combined with existing chemotherapy drugs such as cisplatin, 5-fluorouracil, doxorubicin, etc., it can produce a synergistic effect, reduce the dosage and toxic side effects of each drug, and reverse multidrug resistance.

Clinical application prospects and prospects

The transition of aloe emodin from laboratory research to clinical translation presents both opportunities and challenges.

1. Potential clinical application directions：

   • Antitumor adjuvant therapy As a sensitizer for chemotherapy or radiotherapy, or for the treatment of multidrug-resistant tumors. For tumors such as Burkitt's lymphoma, liver cancer, and colorectal cancer that have shown initial therapeutic effects, priority may be given to their development.
   • Dermatology applications Develop topical formulations for acne, dermatitis, burns, and skin infections by utilizing their anti-inflammatory, antibacterial, and wound healing properties.
   • Antiviral applications As a potential drug against influenza virus and other viruses, it is worth further exploration.
   • Functional food/health products As a raw material with antioxidant and immune regulatory functions at a safe dose.

2. challenges faced：

   • Low bioavailability This is the biggest obstacle to the development of its oral formulations.
   • Complex mechanism of action The multi-target characteristic is not only advantageous (less prone to drug resistance), but also requires more precise elucidation of its main target and signaling network.
   • Potential toxicity The safety of long-term use, especially genetic toxicity and organ toxicity, requires more systematic and standardized preclinical and clinical evaluations.
   • Quality and Standardization of Medicinal Materials The content of aloe emodin from plant sources is affected by variety, origin, harvest season, and processing methods, and strict quality control standards need to be established.

3. Future research prospects：

   • In depth mechanism research Using proteomics, metabolomics, chemical proteomics and other technologies, systematically reveal its direct targets and network pharmacology mechanisms.
   • Strengthen conversion research Conduct comprehensive preclinical pharmacological and toxicological evaluations that comply with Good Laboratory Practice (GLP), and design a reasonable clinical research protocol.
   • Focusing on innovative dosage forms Vigorously developing targeted delivery systems based on nanotechnology is the key path to achieving clinical breakthroughs.
   • Explore combination therapy strategies Systematically study the optimal combination scheme and mechanism with existing therapies.

Conclusion

Aloe emodin, as a natural hydroxy anthraquinone derived from traditional medicinal plants, has become a hot molecule in modern natural product pharmacology research due to its extensive anti-tumor, antiviral, anti-inflammatory and other pharmacological activities. Its mechanism of action involves inducing cell apoptosis, cycle arrest, inhibiting metastasis and angiogenesis, and achieving multi-target regulation by intervening in multiple key signaling pathways such as mTORC2, PI3K/Akt, NF - κ B. However, drug defects such as poor solubility and low bioavailability, as well as long-term safety issues that need to be clearly defined, constrain its direct translation into clinical drugs. In the future, through structural optimization, innovative drug delivery system development, and rational combination therapy strategies, it is expected to overcome these bottlenecks. With the continuous deepening of understanding of its molecular mechanism and the advancement of formulation technology, aloe emodin is expected to develop from a promising lead compound into a new drug or effective adjuvant for the treatment of major diseases such as tumors, demonstrating the sustained vitality of natural products in the field of drug research and development.