Synonym name:
Catalogue No.: BP0756
Cas No.: 33676-00-5
Formula: C24H30O7
Mol Weight: 430.497
Botanical Source: Phyllanthus niruri, Phyllanthus amarus and Phyllanthus urinaria
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:
Hypophyllanthin and phyllanthin have antitumour effects against Ehrlich Ascites Carcinoma in mice. Hypophyllanthin can modulate the vascular tension via the endothelium-independent mechanisms, it can directly inhibit P-gp activity and does not interfere with MRP2 activity, it may reversibly inhibit P-gp function. Hypophyllanthin offers a promising means for treatment of chronic muscle pain. Hypophyllanthin also has estrogenic properties against carbofuran induced toxicity in female rats.
References:
J Pharm Pharmacol. 2013 Feb;65(2):292-9.
Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cells.
The purposes of this study were to investigate the inhibitory effects of two lignans, phyllanthin and Hypophyllanthin, on the function of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2), using the in-vitro model of Caco-2 cells. In addition, the effect of prolonged exposure to these two compounds on the expression of active P-gp was also determined.
METHODS AND RESULTS:
The activity of P-gp and MRP2 was determined in the uptake assays by monitoring the intracellular accumulation of their specific substrates (calcein acetoxymethyl ester and 5(6)-carboxy-2',7'-dichlorofluorescein diacetate, respectively) with fluorescence spectroscopy. Hypophyllanthin and phyllanthin inhibited P-gp function with comparable potencies, but neither compound affected MRP2 activity. When the lignans were washed out before addition of substrate, the inhibitory action of both compounds against P-gp function was lost. These results suggested the reversibility of the inhibition. Moreover, prolonged exposure of the Caco-2 cells to both lignans (up to 7 days) had no effect on P-gp function.
CONCLUSIONS:
Phyllanthin and Hypophyllanthin directly inhibited P-gp activity and did not interfere with MRP2 activity. It was likely that both phyllanthin and Hypophyllanthin could reversibly inhibit P-gp function.
Fitoterapia. 2011 Dec;82(8):1231-6.
Endothelium-independent effects of phyllanthin and hypophyllanthin on vascular tension.
The purpose of this study was to investigate the modulating effects of phyllanthin and Hypophyllanthin on vascular tension, using in the in vitro model of isolated rat aorta.
METHODS AND RESULTS:
Our results indicated that both phyllanthin and Hypophyllanthin significantly relaxed the sustained contraction induced by phenylephrine (PE) in a concentration-dependent manner. In addition, endothelial removal had no significant influence on the vasorelaxation responses of the aortic rings toward these two compounds. Furthermore, both compounds inhibited the contraction of aortic muscle provoked by either PE (1 μM) or KCl (40 mM) as well as the spontaneous contraction of the Ca²⁺-depleted muscle. In high K⁺-Ca²⁺ free solution, phyllanthin (100 μM), but not Hypophyllanthin, significantly inhibited the contractile responses upon cumulative addition of CaCl₂. Both compounds (100 μM) significantly inhibited PE-induced contraction in Ca²⁺-free condition, but could not affect caffeine-induced contraction.
CONCLUSIONS:
Taken together, phyllanthin and Hypophyllanthin could modulate the vascular tension via the endothelium-independent mechanisms. The modulating effects of both compounds were possibly involved with the blockade of Ca²⁺ entry into vascular smooth muscle cells and inhibition of PE-mediated Ca²⁺ release from sarcoplasmic reticulum.
Phytother Res. 2015 Aug;29(8):1202-10.
Pain Modulation by Lignans (Phyllanthin and Hypophyllanthin) and Tannin (Corilagin) Rich Extracts of Phyllanthus amarus in Carrageenan-induced Thermal and Mechanical Chronic Muscle Hyperalgesia.
The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and Hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain.
METHODS AND RESULTS:
Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration.
CONCLUSIONS:
In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, Hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Hypophyllanthin is a major natural lignin product isolated from plants of the Phyllanthus genus, which exhibits significant biological activity, particularly in the fields of anti-inflammatory and anti-tumor effects. Phyllanthus plants are widely used in traditional medicine to treat various diseases such as liver disease, inflammation, and viral infections. Phyllanthus, as one of its important active ingredients, has received high attention in pharmacology and natural product chemistry in recent years. Research has shown that Yaxiazhusu not only effectively inhibits P-glycoprotein (P-gp) activity and improves drug tolerance, but also plays a key role in the molecular mechanisms of various diseases such as liver cancer. This article will provide a systematic review of the chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity, mechanism of action and molecular targets, pharmacological evaluation and pharmacokinetic characteristics of Phyllanthus tinctorius, and explore its clinical application prospects and future research directions.
The chemical structure of Hypophyllanthin belongs to lignin compounds, with a molecular formula of C25H30O7 and a molecular weight of 430.4970. Its structural features include multiple aromatic rings and methoxy substituents, endowing it with strong lipid solubility and biological activity. The LogP value of Yaxia Zhuci Su is 3.9290, indicating that it has good lipid solubility and is beneficial for penetrating cell membranes and the blood-brain barrier (BBB). The predicted value of the latter is high, indicating its potential application value in central nervous system diseases.
The polar surface area (TPSA) is 64.6100, and moderate polarity facilitates its binding to biomolecule targets. The low water solubility (0.0078 mg/mL) poses a certain challenge to its drug formulation design, and its bioavailability needs to be improved through techniques such as nanocarriers or liposomes. Toxicological evaluation shows that Phyllanthus tinctorius does not inhibit hERG channels, and the Ames test result is 0.0, indicating a low genetic toxicity risk and good safety.
Phyllanthus niruri and Phyllanthus urinaria, medicinal plants such as Phyllanthus niruri and Phyllanthus urinaria, are mainly found in Phyllanthus genus plants. Phyllonthus plants are widely distributed in tropical and subtropical areas, and are traditionally used to treat hepatitis, kidney disease, inflammation and infectious diseases.
The common methods for extracting Phyllanthus tinctorius include solvent extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. Generally, methanol or ethanol is used as the extraction solvent, and the extraction efficiency is improved by ultrasound assisted extraction or reflux extraction. Subsequently, separation and purification were carried out using silica gel column chromatography or reverse phase C18 column, and the purity and structure were confirmed by HPLC and mass spectrometry. In recent years, supercritical CO2 extraction and membrane separation technologies have also been explored and applied to the efficient extraction of chlorophyll from leaves, in order to achieve industrial production.
The anti-inflammatory effect of Yaxia Zhuci Su is one of its earliest discovered pharmacological activities. Both in vitro and in vivo studies have shown that resveratrol can significantly inhibit the production of inflammatory mediators, such as prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF - α), and interleukin-6 (IL-6). The anti-inflammatory mechanism mainly involves inhibiting the expression of cyclooxygenase-2 (COX-2, PTGS2 gene products) and activating the NF - κ B signaling pathway, thereby reducing the inflammatory response.
Yaxia Zhuci Su exhibits potential multi-target anticancer activity in the field of tumor therapy, especially in liver cancer models. Research has shown that Phyllanthus tinctorius can regulate various signaling pathways related to liver cancer, including inhibiting the STAT3, MAPK1, PI3K/AKT pathways, regulating the expression of tumor suppressor gene TP53 and anti apoptotic protein BCL2. In addition, Yaxiazhusu can downregulate matrix metalloproteinase 9 (MMP9) and epidermal growth factor receptor (EGFR), inhibiting the invasion and metastasis ability of tumor cells.
Yexiazhusu can directly inhibit the activity of P-glycoprotein (P-gp) without interfering with multidrug resistance associated protein 2 (MRP2), providing a new strategy for overcoming drug tolerance in tumor cells. As an important drug efflux pump, the inhibition of P-gp activity helps to increase the accumulation of chemotherapy drugs in tumor cells and enhance therapeutic efficacy.
Some studies have also reported that Yaxiazhusu has antioxidant, antiviral, and neuroprotective effects, especially its ability to penetrate the blood-brain barrier, making it potentially applicable in central nervous system diseases.
The pharmacological effects of Yaxia Zhuci Su involve multiple signaling pathways and key molecular targets, especially in the treatment of liver cancer. Its main mechanism of action includes:
Regulating cell apoptosis and proliferation
Yaxia Zhuci Su promotes tumor cell apoptosis by regulating the expression of BCL2 family proteins. Its activation effect on TP53 enhances cell cycle arrest and DNA repair, and inhibits abnormal cell proliferation.
Inhibiting signal transduction pathways
Yaxia Zhuci Su can inhibit the STAT3 and MAPK1 signaling pathways, blocking the growth signal transmission of tumor cells. The PI3K/AKT pathway related to PIK3CA is also regulated, further inhibiting cell survival and migration.
Inhibit tumor invasion and metastasis
By downregulating the expression of MMP9 and EGFR, Yaxiazhusu reduces the degradation and invasion ability of tumor cell matrix, and inhibits tumor metastasis.
Anti inflammatory and immune regulation
Yaxia Zhuci Su inhibits the expression of PTGS2 (COX-2), alleviates inflammatory reactions in the tumor microenvironment, improves immune cell function, and enhances anti-tumor immunity.
Overcoming drug tolerance
Directly inhibit P-gp activity, block drug efflux, increase intracellular concentration of chemotherapy drugs, and enhance tumor cell sensitivity to drugs.
The pharmacological parameters of Yaxia Zhuci Su indicate that it has certain potential for drug development. A higher LogP value and moderate TPSA are beneficial for its cell membrane penetration and biological activity. The high permeability of the blood-brain barrier suggests its advantages in the treatment of central nervous system diseases. In terms of safety, it does not inhibit hERG channels and has no genetic toxicity risk, providing a good foundation for its clinical development.
However, the low water solubility of Yaxiazhusu limits its oral bioavailability and formulation development, and needs to be improved through chemical modification or novel drug delivery systems. There is currently limited research on pharmacokinetics in vivo, and in the future, systematic studies on its absorption, distribution, metabolism, and excretion (ADME) characteristics should be strengthened to clarify key parameters such as in vivo stability and half-life.
As an important active ingredient in plants of the Phyllanthus genus, Yaxiazhusu has shown broad clinical application prospects due to its multi-target anti-inflammatory, anti-tumor, and anti drug tolerance effects. Especially in the field of liver cancer treatment, it provides a potential adjuvant therapy strategy by regulating multiple signaling pathways and key molecular targets. In addition, the inhibitory effect of Yaxiazhusu on P-gp provides a new approach to overcome multidrug resistance, which may be combined with existing chemotherapy drugs to improve efficacy.
Future research should focus on the pharmacokinetic optimization, formulation development, and safety evaluation of Yaxiazhusu, in order to promote its transition from laboratory research to clinical application. At the same time, combining modern molecular biology techniques, we will deeply analyze its mechanism of action, screen for more selective derivatives, and enhance its efficacy and safety. The implementation of multicenter clinical trials will be a key step in verifying their clinical value.
As a natural lignin with significant anti-inflammatory and anti-tumor activities, Yaxiazhusu has shown important potential in the treatment of liver cancer and related diseases due to its unique chemical structure and multi-target mechanism of action. Its good safety and pharmacological parameters lay the foundation for subsequent drug development. In the future, through interdisciplinary collaboration, optimizing its drug properties and conducting systematic clinical research, it is expected to develop Yaxiazhusu into a new natural product drug, providing new options for the treatment of liver cancer and other major diseases.
