Traditional Herbal Extracts Research Articles

Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1-7) Axis and Decreasing Inflammation Responses in Rats.

Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.

The in vitro antifungal activity of 30 Chinese herb extracts to Saprolegnia sp.

Summary Chinese traditional medicines have been used for several thousands of years in Asian countries, not only in humans but also in many animal species. These compounds prevent and control different types of diseases including internal diseases as well as some infectious diseases, where the aetiological agent is viral, bacterial, parasitic or mycotic. Rhizoma coptidis is believed to inhibit Shigella dysenteriae and that Radix isatidis can prevent flu caused by the influenza virus. It is thus hypothesized that some of these traditional herbal compounds will have anti-fungal activity. Saprolegniosis is a disease common in fish and their eggs in both fresh and brackish water; a newer, safer medication against Saprolegnia is needed after the prohibition in many countries of the extremely effective fungicide, malachite green. In the present study an attempt is made to identify herbal compounds that have anti-Saprolegnia activity. A strain of Saprolegnia, CCF1301, was isolated from the skin of infected grass carp (Ctenopharyngodon idella) and identified as Saprolegnia ferax by the 26S rDNA D1/D2 region and ITS region. This strain was used to evaluate the antifungal activity of thirty Chinese traditional herbal medicine extracts, and a modified dish dilution method was developed for the evaluation. Saprolegnia-infected rapeseeds with visible hyphae were transplanted onto prepared PDA plates containing 2 g L−1 herbal plant extracts and incubated at 20°C for 48 h. Each herbal plant species was tested in triplicate. Those herbal plant extracts that showed negative mycelium presence at 2 g L−1 were further tested for minimum inhibitory concentration (MIC) evaluation. The results showed that Syzygium aromaticum, Magnolia officinalis, Melaphis chinensis, Euphorbia fischeriana Steud, and Sophora flavescentis exhibited enhanced growth inhibition at 2 g L−1 and MIC values of 500, 62.5, 250, 62.5, 250 mg L−1 concentrations, respectively. It was obvious that Magnolia officinalis and Euphorbia fischeriana Steud exhibited the best antifungal activity. Since there is a high natural toxicity in Euphorbia fischeriana Steud, its applicability as the main ingredient in an aquaculture therapeutic formulation requires further research. Thus, Magnolia officinalis would appear to be the more valuable antifungal herbal species with which to pursue further research.

Methodology to nanoencapsulate hepatoprotective components from Picrorhiza kurroa as food supplement

Abstract Picrorhiza kurroa root and rhizome powder of extract is well-recognized neutraceutical for healthy liver functioning. The major hepatoprotective components (picrosides I and II) of P. kurroa extract shows poor intestinal absorption and poor bioavailability due to sparingly aqueous solubility. To improve bioavailability of these biomolecules, a nanoformulation of this extract has been developed with pluronic-F-68 copolymer based biodegradable PLA nanoparticles by nanoprecipitation method. This method showed high encapsulation efficiency as 60.1±2.8% (for picroside I) and 67.2±7.4% (for picroside II). The hydrodynamic (by zeta size) and actual size (by TEM) revealed homogenously rounded nanoparticles of size 174±34 nm and 154±12 nm respectively. This formulation showed an initial burst and half release up to 27±3 h, followed by a sustained release (up to 210±10 h). Nanoformulation of this traditional herbal extract provides neutraceutical with value addition property for better hepato-protection by enhancing intestinal absorption and bioavailability.

Is synthetic mouthwash the final choice to treat oral malodour?

The aim of the review was to critically appraise the various pros and cons of the synthetic and herbal agents used in mouthwashes against halitosis and facilitate users to choose appropriate mouthwashes according to their need. Oral Malodour (OMO) or halitosis is a global epidemic with social and psychological impact. Use of mouthwash has been adopted worldwide to control halitosis within a past few decades. Alcohol and Chlorhexidine are common agents in synthetic mouthwashes, while Tannins and Eugenol are derived traditional herbal extracts. Each agent signifies some unique properties distinguishing them from others. Herbal ingredients are gaining the attention of the profession due to its mild side effects and competitive results. Herbal mouthwashes can be a safer choice in combating OMO, as an alternate to synthetic mouthwashes.

Hydroxypropyl Methylcellulose Reduces Particle Adhesion and Improves Recovery of Herbal Extracts During Spray Drying of Chinese Herbal Medicines

The effectiveness of hydroxypropyl methylcellulose (HPMC) as an anti-adherent during spray drying of traditional Chinese herbal extracts was explored. A small amount of HPMC (minimum concentration 8%) was sufficient to overcome problematic particle adhesion, whereas a large amount of maltodextrin (50%) was required for the same effect. HPMC exerted a strong anti-adhesive effect that was independent of the type of HPMC, raw materials used, and the process used to synthesize HPMC. The anti-adhesion mechanism was studied through an analysis of the surface tension of the prepared solutions before spray drying, the glass transition temperature (T g ), and X-ray photoelectron spectroscopy (XPS) of spray-dried powders. The T g of powders containing more than 8% HPMC was approximately 40°C and did not increase linearly with the HPMC concentration. The surface tension of Crataegi fructus extract was 54.1 ± 0.2 mN/m and further decreased to 46.6 ± 0.2 mN/m upon addition of HPMC to 24%. When the concentration of HPMC increased to 8%, potassium could not be detected on the surface of dried powders by XPS. These results suggest that modification of the surface properties of sprayed droplets/particles by HPMC increased the HPMC surface coverage of the particles and reduced adhesion during spray drying.

Cyclosporine and Herbal Supplement Interactions

Cyclosporine (CyA) is a well-known immunosuppressant with a narrow therapeutic window. Its bioavailability is affected by many other traditional drugs and herbal extracts. Cytochrome P-450 isoenzymes CYP3A4 and CYP3A5 and protein P-glycoprotein (P-gp) are involved in CyA bioavailability. Interactions of CyA with herbal extracts are not well known, but, given their increased concomitant use, it is important to know which extracts, many of which are commonly self-prescribed, can affect CyA blood concentrations. Decreased CyA blood concentration has been shown with St John's wort in case reports and, in vivo animal studies, with ginger, liquorice, scutellariae radix, and quercetin. Increased CyA concentration has been reported in patients with grapefruit juice, chamomile, or berberine, and with cannabidiol or resveratrol in animal studies. Effects of Echinacea and Serenoa repens on CyA levels have not been shown consistently, but concomitant use should be avoided. Although findings from animal studies cannot be directly translated into humans, avoiding concomitant use of herbal extracts is prudent until human clinical studies have ruled out any possible interaction. Clinicians should interview their patients carefully about their use of herbal supplements before CyA administration, and those receiving CyA should be warned about possible interactions between herbal preparations and CyA.

Abstract P6-09-08: Withania somnifera extract inhibits invasion and metastasis of MDA-MB-231 cells by inhibiting CCL2 and CD44 high/CD24low stem cells

Abstract Standard approaches to the treatment of cancer, including surgery, chemotherapy, and radiation, when used alone or in combination, have had limited efficacy in curing the disease. These treatments frequently produce debilitating side effects, such as nausea, vomiting, loss of hair, and suppression of immunity. Due to these side effects, interest in other cancer treatments, including herbal extracts, has increased. Traditional herbal extracts are considered to be safe and economically feasible as alternative medicines to treat cancer. An alcoholic extract of the roots of Withania somnifera (WS), a traditional herbal remedy, has immunostimulatory, radiosensitizing, and anticancer effects. Knowledge of the medicinal properties of this plant motivated us to investigate its efficacy as an antitumor agent against breast cancer MDA-MB-231 human breast cancer cells were used as a model. Tests included an MTT assay for cell viability, an assay for testing of migration of cancer cells, PCR analysis for cytokines, evaluation of gene expression, an immunohistopathological assay for expression of cytokines in isolated tissues, and xenografts in nude mice to evaluate inhibition of tumor growth. In cell cultures, WS showed antiproliferative and anti-invasive effects against MDA-MB-231 breast cancer cells; it also inhibited the metastasis of xenografted MDA-MB-231 cells to the lungs of treated mice. These findings were substantiated in vitro by use of a microarray technique. WS caused down-regulation of cytokines CCL2, CXCL1, CXCL2, CXCL3, IL-1b, and TGF-β3. CCL2 is the cytokine considered to be most responsible for the metastasis of breast cancer cells. The inhibition of CCL2 by WS was confirmed in sections of xenografted treated tumors and in cell culture by use of immunohistochemical and flow cytometry techniques, respectively. WS caused 50% inhibition of CD44-bearing breast cancer stem cells, the predominant stem cells of the MDA-MB-231 breast cancer cell line. This finding will be further pursued by sorting CD44high/CD24low stem cells by use of flow cytometry. In summary, WS caused inhibition of proliferation and invasion of breast cancer cells in culture and growth of xenografted cancer cells in mice. These effects may be associated with inhibition of cytokines such as CCL2 and CD 44high/CD 24low s. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-08.

경동맥 혈전 유발 동물모델을 이용한 한약재 추출물의 효능 검색

Objectives : The aim of this study was to examine anti-thrombotic effect of traditional herbal extracts in a rat model of ferric chloride (<TEX>$FeCl_3$</TEX>)-induced carotid arterial thrombosis. Methods : Thirty minutes prior to a 35% <TEX>$FeCl_3$</TEX> application, Sprague Dawley(SD) rats were injected with the 10 types of traditional herbal extracts (100mg/kg, intraperitoneal injection), respectively. The effect of these herbal extracts was examined for time to occlusion(TTO) using the Laser doppler flow meter and measured for thrombus weight (TW) in <TEX>$FeCl_3$</TEX>-induced thrombosis model. Results : In the TTO, Salvia miltiorrhiza (Sm, <TEX>$2.30{\pm}0.28$</TEX> min, p<0.001) and Santalum album (Sa, <TEX>$2.19{\pm}0.19$</TEX> min, p<0.001) showed significantly delayed TTO more than twice compared with Saline-treated group. Cnidium officinale (Co), Psoralea corylifolia (Pc), Scutellatia baicalensis (Sba), Panax notoginseng (Pn), Angelica tenuissima (At), Scrophularia buergeriana (Sbu), Rhus verniciflua (Rv) and Picrasma quassioides (Pq), except for Rhus verniciflua (Rv) also meaningfully impeded TTO more than one fold. In addition, Salvia miltiorrhiza, Santalum album, Cnidium officinale, Psoralea corylifolia and Scutellatia baicalensis significantly reduced TW more than 10% compared with Saline-treated group. Especially, Salvia miltiorrhiza and Santalum album showed the most excellent anti-thrombotic effect among the 10 herbal extracts tested on the restoration of altered TTO and TW. Conclusions : These results suggest that Sm and Sa extracts have outstanding anti-thrombotic effect in <TEX>$FeCl_3$</TEX>-induced thrombosis model and is potentially useful as herbal medicines for the treatment and prevention of thrombosis.

Study on the performance enhancement of lime mortar used in ancient temples and monuments in India

Lime is arguably the world first true green and versatile building material. The traditional lime binder offers greater durability but less strong compared to cement. The objective of the study is to improve the strength parameters of lime using traditional herbs. Lime mortar prisms (mix proportion: 1:2 i.e., one part of lime to 2 parts of sand) were cast after 15 days of fermentation with traditional herbal extract [aqueous extract of oonjalvalli ( Cissus glauca Roxb.), pananchikaai ( Cochlospermum religiosum ), kulamavu ( Persea macrantha ), gallnut ( Terminalia chebula ) and palm jaggery (from Borassus flabellifer )] and tested for its Flexure, Tension and Compressive strengths. The lime mortar prism fermented with plain water was used as control. The transverse strength of herbal lime mortar (5% herbs) is 1.6 times greater than lime mortar fermented with plain water. Besides, there was an increase in the tensile strength by three folds, due to elastic nature of herbal lime mortar. The compressive strength is greatly enhanced up to 2.5 times on the addition of 5% herbs. This may be due to the fact that herbal extract enhanced the density of lime mortar by bringing the particles of lime mortar closer to each other, thereby producing a more compact mass. Traditional structures built with lime mortar, which are more than 4,000 years old like Mohanjo-Daro is still a heritage monument of Indian civilization. It is more appropriate to blend the traditional concept with modern structures. The present work may also help in reviving ancient monuments.

The extracts of Fructus Akebiae, a preparation containing 90% of the active ingredient hederagenin: Serotonin, norepinephrine and dopamine reuptake inhibitor

Fructus Akebiae is a traditional Chinese herbal extract that has been used for the treatment of depressive disorders in China. Previous studies demonstrated that Fructus Akebiae extracts (FAE) displayed a potent antidepressant-like activity in animal behavior tests and found that the specific active ingredient from the extracts of Fructus Akebiae is hederagenin. However, the underlying mechanism is unknown. Here we provide evidences that FAE enhances the signaling of central monoamines via inhibition of the reuptake of the extracellular monoamines including serotonin (5-HT), norepinephrine (NE) and dopamine (DA). In rat brain membrane preparations and HEK293 cells transfected with human serotonin transporter (SERT), NE transporter (NET) and DA transporter (DAT), we found that FAE displayed marked affinity to rat and cloned human monoamine transporters in ex vivo and in vitro experiments, using competitive radio ligand binding assay. In uptake assays using rat synaptosomes and transfected cells, FAE was found to significantly inhibit all three monoamine transporters in a dose- and time-dependent manner, with a comparable or better potency to their corresponding specific inhibitors. In contrast, FAE (10μM), showed no significant affinity to a variety array of receptors tested from CNS. In support of our uptake data, in vivo microdialysis studies showed that administration of FAE (12.6, 25, 50mg/kg) significantly increased extracellular concentrations of 5-HT, NE and DA in frontal cortex of freely moving rats. Taken together, our current study showed for the first time that FAE is a novel triple inhibitor of monoamine transporters, which may be one the mechanisms of its antidepressant activity.

Chan-Yu-Bao-Yuan-Tang, the Water Extract of a Chinese Medicine Prescription, Induces S-Phase Arrest and Mitochondria-Mediated Apoptosis in Human Lung Adenocarcinoma Cells

Previous clinical studies have shown good efficacy of the traditional Chinese medicinal herbal water extract Chan-Yu-Bao-Yuan-Tang (CYBYT) in lung cancer patients. In this study, CYBYT's effects on proliferation and apoptosis of human lung adenocarcinoma cell line SPC-A-1 cultured in vitro were explored. An XTT assay, cell cycle analysis, Annexin V-FITC staining and Western blot were applied to identify the viability of cells, cell cycle arrest, stages of apoptosis, and signaling proteins, respectively. The results showed that CYBYT inhibited the growth of SPC-A-1 cells by reducing the cells in G0/G1 phase but increasing them in S phase in a concentration-dependent manner, and inducing apoptosis, whereas it had no significant inhibitory effects on the normal human IMR-90 fibroblasts. Furthermore, early and total induction of apoptosis was positively correlated with the concentration of CYBYT in SPC-A-1 cells, and the rate of total apoptosis was greater in the CYBYT 100 µg/mL and 50 µg/mL groups than that of the positive control 5-fluorouracil (5-Fu) group. Moreover, CYBYT upregulated bax, cleaved caspase-3 protein expression, downregulated bcl-2 protein expression, and released mitochondrial cytochrome c into the cytosol in a time- and concentration-dependent manner. Our findings indicated that CYBYT could significantly inhibit growth and induce apoptosis via the mitochondrial pathway in human lung adenocarcinoma cell line SPC-A-1.

Chan-Yu-Bao-Yuan-Tang and 5-fluorouracil synergistically induce apoptosis by means of the caspase-3 signaling pathway in lung and cervical cancer cells

Previous clinical studies have shown the safety and efficacy of the traditional Chinese medicinal herbal aqueous extract Chan-Yu-Bao-Yuan-Tang (CYBYT) for the treatment of lung and cervical cancer patients. Used in combination with 5-fluorouracil (5-Fu), CYBYT has been observed to be particularly effective in cancer treatment. Herein, the combined anticancer effect and the underlying mechanisms of 5-Fu and CYBYT in the human lung cancer cell line A549 and the human cervical cancer cell line HeLa were investigated invitro. The MTT assay, Annexin V-FITC staining and Western blotting were applied to identify cell viability, the stages of apoptosis and the expression of signaling proteins, respectively. The results indicated that CYBYT and 5-Fu, alone or in combination, significantly inhibited proliferation and induced marked apoptosis in A549 and HeLa cells, but had no significant inhibitory effects on normal human IMR-90 fibroblasts. The rate of mid and late apoptosis or necrosis was greater after 5-Fu treatment compared to treatment with CYBYT or the combination of agents; however, the early apoptotic rate showed opposite results. CYBYT and 5-Fu, alone or in combination, up-regulated cleaved caspase-3 expression in a time-dependent manner, with CYBYT being more effective than 5-Fu. Taken together, our data show that the pro-apoptotic activity of the two-drug combination was much stronger than that of CYBYT or 5-Fu alone; CYBYT combined with 5-Fu had synergistic effects at lower concentrations and promoted apoptosis, while the combined treatment also decreased the cytotoxic side effects of 5-Fu.

Medicinal herbal extracts of Sophorae radix Acanthopanacis cortex Sanguisorbae radix and Torilis fructus inhibit coronavirus replication in vitro

Cimicifuga rhizome, Meliae cortex, Coptidis rhizome and Phellodendron cortex have been previously shown to exhibit anti-coronavirus activity. Here, an additional 19 traditional medicinal herbal extracts were evaluated for antiviral activities in vitro. A plaque assay was used to evaluate the effects of 19 extracts, and the concentration of extract required to inhibit 50% of the replication (EC(50)) of mouse hepatitis virus (MHV) A59 strain (MHV-A59) was determined. The 50% cytotoxic concentration (CC(50)) of each extract was also determined. Northern and western blot analyses were conducted to evaluate antiviral activity on viral entry, viral RNA and protein expression, and release in MHV-infected DBT cells. Sophorae radix, Acanthopanacis cortex and Torilis fructus reduced intracellular viral RNA levels with comparable reductions in viral proteins and MHV-A59 production. The extracts also reduced the replication of the John Howard Mueller strain of MHV, porcine epidemic diarrhoea virus and vesicular stomatitis virus in vitro. Sanguisorbae radix reduced coronavirus production, partly as a result of decreased protein synthesis, but without a significant reduction in intracellular viral RNA levels. The EC(50) values of the four extracts ranged from 0.8 to 3.7 microg/ml, whereas the CC(50) values ranged from 156.5 to 556.8 microg/ml. Acanthopanacis cortex and Torilis fructus might exert their antiviral activities in MHV-A59-infected cells by inducing cyclooxygenase-2 expression via the activation of extracellular signal-related kinase (ERK) and p38 or ERK alone, respectively. Sophorae radix, Acanthopanacis cortex, Sanguisorbae radix and Torilis fructus might be considered as promising novel anti-coronavirus drug candidates.

In vitro inhibition of coronavirus replications by the traditionally used medicinal herbal extracts, Cimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, and Phellodendron cortex

BackgroundA search for new anti-coronaviral drugs to treat coronaviral infections was motivated by an outbreak of severe acute respiratory syndrome (SARS). ObjectivesIn order to find drugs that treat coronavirus infections, including SARS, we screened traditional medicinal herbal extracts and evaluated their antiviral activities on coronavirus replication. Study designWe employed a plaque assay to evaluate the effect of 22 medicinal herbal extracts on virus replication. We determined the 50% effective concentration (EC50) of each extract that was necessary to inhibit the replication of mouse hepatitis virus A59 (MHV-A59); we also determined 50% cytotoxic concentrations (CC50) for each extract. Northern and Western blot analyzes were performed to investigate antiviral activity in MHV-infected DBT cells, including virus entry, viral RNA and protein expression, and virus release. Coronavirus specific inhibition was also demonstrated using porcine epidemic diarrhea virus (PEDV). ResultsCimicifuga rhizoma, Meliae cortex, Coptidis rhizoma, Phellodendron cortex and Sophora subprostrata radix decreased the MHV production and the intracellular viral RNA and protein expression with EC50 values ranging from 2.0 to 27.5μg/ml. These extracts also significantly decreased PEDV production and less dramatically decreased vesicular stomatitis virus (VSV) production in vitro. ConclusionsThe extracts selected strongly inhibited MHV replication and could be potential candidates for new anti-coronavirus drugs.

Effects of Erxian Decoction and its separate prescriptions on the levels of luteinizing hormone and follicle-stimulating hormone in anterior pituitary cells from female rats

To investigate the effects of Erxian Decoction (EXD), a traditional Chinese compound herbal medicine and its separate prescriptions such as Wenshen Yijing Recipe (WSYJR, a recipe for warming kidney and replenishing essence), Ziyin Xiehuo Recipe (ZYXHR, a recipe for nourishing yin and dispersing fire) and Tiaoli Chongren Recipe (TLCRR, a recipe for regulating thoroughfare and conception vessels) and some extracts from EXD on the levels of LH and FSH in the primary cultured anterior pituitary cells from female rats. EXD, its separate prescriptions and traditional Chinese herbal extracts from EXD were added directly to the incubators. The levels of LH and FSH were tested by radioimmunoassay. The levels of LH and FSH in the supernatant of anterior pituitary cells treated by EXD or its separate prescriptions including ZYXHR and TLCRR were increased significantly as compared with those in the blank control. There was a tendency for stimulating the secretions of LH and FSH in the WSYJR-treated group too. Dimethyl sulfoxide as the solvent of icariin and curculigoside could interfere with the results. EXD and its separate prescriptions such as ZYXHR and TLCRR can increase the levels of LH and FSH significantly.

Traditional Indian herbal extracts used in vitroagainstgrowthofthepathogenicbacteria–Aeromonashydrophila

Crude ethanol extracts of Acalypha indica, Acorus calamus, Coleus aromaticus, Heliotropium indicum, and Indigofera aspalathoides were screened for antibacterial activity in vitro against the growth of the fish pathogenic bacteria, Aeromonas hydrophila. Terramycin, widely used to con- trol A. hydrophila in aquaculture, was used as a positive control. The herbs A. calamus and I. aspalathoides warded off the growth of the pathogen completely at minimum inhibitory concen- trations of 1.29 and 2.16 mg/l, respectively. A minimum bacterial concentration of 1.00 cfu occurred at concentrations of 0.77 mg/ml for A. calamus and 1.29 mg/ml for I. aspalathoides. The order of potency of the herbs in warding off growth of A. hydrophila in vitro was ranked: A. calamus, I. aspalathoides, C. aromaticus, A. indica, and H. indicum. The inhibitory potency of A. calamus and I. aspalathoides was significantly higher (p&lt;0.05) than that of the positive control, indicating the potential of these herbs to replace antibiotics in controlling A. hydrophila infection.

Antioxidant and genotoxic properties of South African herbal extracts

This study investigated the antioxidant and genotoxic properties of 13 South African herbal extracts. Results from the single-cell gel electrophoresis (Comet) assay indicated that there were profound differences between the plant extracts in their ability to produce DNA damage, which varied from highly genotoxic to protective. Similarly, water and methanol extracts of all the herbal preparations showed variable potencies in scavenging hydroxyl radicals, as measured by means of electron spin resonance spectrometery (ESR) with the spin trap α-phenyl- N-tert-butylnitrone (PBN). In general, methanol extracts were better scavengers of hydroxyl radicals than the corresponding water extracts. This was also true of the ability of these extracts to inhibit membrane lipid peroxidation, assessed with diphenyl-1-pyrenylphosphine (DPPP). However, neither methanol nor water extracts had the ability to protect against DNA damage. The results show that further research on South African traditional herbal extracts is imperative to gain understanding of the mechanisms involved in their pharmacological effects. The tests implemented in the present investigation are recommended for screening other herbal extracts.

Chronic liver injury, TGF-β, and cancer

Cells termed myofibroblasts are prominent in the injury response of all epithelial tissues. They exhibit proliferation, migration, production of collagen and other extracellular matrix (ECM) molecules, and contraction, all for containing the injury and closing the wound. When the injury is limited in time, the final stage of the repair involves a dismantling of the cellular apparatus and restoration of normal tissue structure. With multiple cycles of repair, however, there is net accumulation of ECM, to the detriment of tissue structure and function. Repair-related ECM coalesces into fibrous bundles and, over time, undergoes changes that render it resistant to degradation. The result is a scar. In the skin, a scar may have cosmetic importance only. In the liver, however, extensive scarring is the setting for unregulated growth and neoplasia; also, fibrous bands disrupt normal blood flow, leading to portal hypertension and its complications. With regard to therapy for fibrosis, the first consideration is elimination of the injury factor. However, given that many liver diseases do not have effective therapies at present, strategies targeting fibrogenesis per se are under development. The main source of myofibroblast-like cells and ECM production in the liver is the perisinusoidal stellate cell, which responds to injury with a pleiotypic change termed activation. Activation is orchestrated by cytokines and the ECM itself. Among the cytokines involved in this process, transforming growth factor-beta (TGF-beta) is particularly prominent. The early changes in ECM include de novo production of a specific "fetal" isoform of fibronectin, which arises from sinusoidal endothelial cells. It is stimulated by TGF-beta and acts directly on stellate cells to promote their activation. Based on these and other advances in understanding the fundamentals of the injury response, several strategies now exist for altering fibrogenesis, ranging from agents that block TGF-beta to traditional Chinese herbal extracts. Arrest of fibrogenesis, even with underlying cirrhosis, is likely to extend life or prolong the time to transplant. Whether it reduces the risk of hepatocellular carcinoma remains to be proven. Although TGF-beta antagonists are effective anti-fibrogenic agents, they will require detailed safety testing because of the finding that several forms of epithelial neoplasia are associated with altered regulation of TGF-beta.