Plants of the genus Terminalia are amongst the most widely used plants for traditional medicinal purposes worldwide. Many species are used for their antibacterial, antifungal, antiprotozoal, antiviral, antidiarrhoeal, analgesic, antimalarial, antioxidant, antiinflammatory and anticancer activities. Wound healing and cardiovascular effects have also been credited to some species. Many Terminalia species have multiple beneficial effects for multiple diseases and ailments. Indeed, the Indian species Terminalia chebula is known as the king of plants in Ayurveda due to its broad range of medicinal uses. However, apart from the reported ethnopharmacological uses of many Terminalia species, surprisingly few studies have rigorously examined this important genus for their medical properties/mechanisms and phytochemistry. This is likely due to the high tannin content common to many Terminalia species and the perception that these tannins may be responsible for much of their beneficial properties. As the complexities of tannins make them poor candidates for drug design, most interest in Terminalia species has been for their pharmacognostic and nutraceutical value and they have often been overlooked as potentials for drug discovery. However, recent reports have identified many other interesting phytochemicals and demonstrated that these may be responsible for several of the reported bioactivities of the Terminalia species used in traditional medicinal systems. The last decade has seen a large increase in the number of studies into the use of Terminalia species as therapeutic agents. Several species used in Ayurvedic medicine (Terminalia arjuna, Terminalia bellerica, Terminalia catappa, T. chebula) in particular have received much recent attention. Similarly, recent reports have also highlighted the medicinal potential of species from Africa, Australia and the Americas. The aim of this report is to summarise the recent research into the medicinal properties, phytochemistry and therapeutic mechanisms of Terminalia species and thus to highlight and direct future areas of research into the medicinal activities of this important genus.

/pdf/the-medicinal-properties-and-phytochemistry-of-plants-of-the-4de1m9s42a.pdf

The medicinal properties and phytochemistry of plants of the genus Terminalia (Combretaceae)

Plants of the genus Aloe have perhaps the longest recorded history of medicinal usage and are amongst the most widely used plants for traditional medicinal purposes worldwide. Aloe vera, Aloe ferox, Aloe arborescens and Aloe perryi are the best known and most widely used, but many other species are also used for their therapeutic properties. The Aloes have been used since ancient times, particularly for the treatment of microbial infections, gastrointestinal disorders and inflammatory conditions. In addition to their myriad uses in traditional therapeutics, the Aloes have also been used as components of cosmetic formulations, and in the food and beverage industries. Despite their wide acceptance, studies from different laboratories often report wide variations in the therapeutic bioactivities from within the same Aloe species, even when the same extraction procedures are used. Furthermore, leaves from individual Aloe plants within the same species may have widely varying levels of the bioactive phytochemicals. Phytochemical analyses have shown that many Aloe species contain various carbohydrate polymers (notably glucomannans) and a range of other low molecular weight phenolic compounds including alkaloids, anthraquinones, anthrones, benzene and furan derivatives, chromones, coumarins, flavonoids, phytosterols, pyrans and pyrones. There has been a wealth of information published about the phytochemistry and therapeutic potential of the Aloes (especially Aloe vera). Much of this has been contradictory. Intra- and interspecies differences in the redox state of the individual Aloe components and in the ratios of these components may occur between individual plants. These factors may all affect the physiological properties of Aloe extracts. Due to the structure and chemical nature of many of the Aloe phytochemicals, it is likely that many of the reported medicinal properties are due to antioxidant or prooxidant effects. The antioxidant/prooxidant activities of many Aloe phytochemicals depend not only on their individual levels, but also on the ratios between the various components and their individual redox states. Therefore, discrepancies between bioactivity studies are likely when using different crude mixtures. This report aims to summarise the phytochemistry of the Aloes and (a) examine how their constituents may be responsible for their medicinal properties and (b) some possible reasons for the wide variations reported for their medicinal properties and (c) their therapeutic mechanisms. Some future areas of research into the medicinal activities of this important genus are also highlighted.

The Genus Aloe: Phytochemistry and Therapeutic Uses Including Treatments for Gastrointestinal Conditions and Chronic Inflammation

Aloe vera has a long history of medicinal usage and its therapeutic properties have been well documented in a variety of bioassays. However, isolated Aloe vera leaf components generally do not display the same bioactivities, or have lower efficacies than crude juice/extracts. It is likely that several components work in a synergistic manner in the crude mixture, resulting in increased bioactivities. Furthermore, different laboratories often report varying bioactivities using the same extraction procedure on plant material from the same species. Individual Aloe vera cultivars may have widely varying levels of the bioactive phytochemicals. Due to the structure and chemical nature of many of the Aloe vera phytochemicals, it is likely that many of its reported medicinal properties are due to anti-oxidant or pro-oxidant effects. The anti-oxidant/pro-oxidant activities of many of Aloe vera's phytochemicals is dependent not only on their individual levels, but also on the ratios of various components, and on their individual redox states. Therefore, discrepencies between bioactivity studies are likely when using different crude mixtures. The potential differences between these crude mixtures need to be taken into account when analysing the reproducibility and efficacy of bioassays of crude extracts.

/pdf/problems-of-reproducibility-and-efficacy-of-bioassays-using-1bb79zr87h.pdf

Problems of Reproducibility and Efficacy of Bioassays Using Crude Extracts, with reference to Aloe vera

Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity. In this study, we investigated the capacity of emodin, an anthraquinone molecule originally extracted from certain natural plants, to prolong transplant survival in a mouse model and explored the cellular and molecular mechanisms underlying its action. We found that emodin significantly extended skin allograft survival and hindered CD3+ T cell infiltration in the allograft, accompanied by an increase in CD4+Foxp3+ and CD8+CD122+ Treg frequencies and numbers but a reduction in effector CD8+CD44highCD62Llow T cells in recipient mice. Emodin also inhibited effector CD8+ T cells proliferation in vivo. However, CD4+CD25+, but not CD8+CD122+, Tregs derived from emodin-treated recipients were more potent in suppression of allograft rejection than those isolated from control recipients, suggesting that emodin also enhances the suppressive function of CD4+CD25+ Tregs. Interestingly, depleting CD25+ Tregs largely reversed skin allograft survival prolonged by emodin while depleting CD122+ Tregs only partially abrogated the same allograft survival. Furthermore, we found that emodin hindered dendritic cell (DC) maturation and reduced alloantibody production posttransplantation. Finally, we demonstrated that emodin inhibited in vitro proliferation of T cells and blocked their mTOR signaling as well. Therefore, emodin may be a novel mTOR inhibitor that suppresses alloimmunity by inducing both CD4+FoxP3+ and CD8+CD122+ Tregs, suppressing alloantibody production, and hindering DC maturation. Thus, emodin is a newly emerging immunosuppressant and could be utilized in clinical transplantation in the future.

/pdf/a-new-immunosuppressive-molecule-emodin-induces-both-cd4-46ja7fn4nw.pdf

A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection.

Advances in immunosuppressive drugs have improved the short-term survival of liver transplantation. However, drug toxicities have been a serious problem in patients after long-term administration. Therefore, it is necessary to develop a novel immunosuppressant with low-toxicity. We investigated the immunosuppressive effects of Emodin on acute graft rejection following liver transplantation in rats. The recipient rats of orthotopic liver transplantation were divided into groups as follows: isograft+NS group, allograft+NS group, and allograft+emodin group. The survival time of the recipients in each group was recorded. Histopathological changes in the liver, as well as serum concentrations of IL-2, TNF-α, and IL-10 and their expressions in liver tissue were determined. Our results showed that Emodin treatment prolonged liver allograft survival time and inhibited histopathologic changes of acute graft rejection. The rejection activity index in groups isograft+NS, allograft+NS, and allograft+emodin were 1.52 ± 0.37, 6.95 ± 0.75, and 4.23 ± 0.51, respectively (P < 0.01, isograft+NS group vs. allograft+emodin group and allograft+NS group vs. allograft+emodin group). The serum levels of IL-2 and TNF-α were down-regulated but that of IL-10 was up-regulated by Emodin. Serum levels of IL-2 and TNF-α were higher in allograft+NS group than the allograft+emodin group, but that of IL-10 showed opposite effects (P < 0.05 or 0.01). Changes in the expression of these cytokines in transplanted liver tissue were consistent with changes in serum concentrations. These results demonstrate that Emodin has therapeutic potentials for alleviating acute rejection following liver transplantation in rats and prolonging liver allograft survival. The mechanisms underlying this effect may be associated with polarizing the Th1/Th2 paradigm to Th2.

https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/ar.21352

Emodin Prolongs Recipient Survival Time After Orthotopic Liver Transplantation in Rats by Polarizing the Th1/Th2 Paradigm to Th2

Objective
To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation.

Effect of emodin in suppressing acute rejection following liver allograft transplantation in rats.

Objective To evaluate the effect of emodin in combination with cyclosporine A(CsA) on rejective reaction against liver graft in rats.Methods The LEW→BN orthotopic liver transplantation rat model was used in the study.A total of 48 rats were divided into 4 groups randomly and equally,after operation they were intraperitoneally injected respectively with normal saline(0.5 mL·d-1,group A);CsA(10.0 mg·kg-1·d-1,group B);emodin(50.0 mg·kg-1·d-1,group C);and CsA plus emodin(group D,at the same dose as in B and C).Six rats taken from each group were sacrificed on the 8th day after operation to calculate the rejection active index(RAI) and hepatocyte apoptosis index(AI).The remainder were stopped medication and used for observing the survival time.Results The inter-group comparisons in mean survival time,RAI and AI showed significant difference in comparing group A with group B,C and D(P0.01),and those in group D were more obvious than in group B and C(P0.05),but showed no significant difference between group B and group C(P0.05).Conclusion Administering of emodin combined with CsA after liver transplantation shows a synergistic effect for suppressing acute rejective reaction in rats.

Synergistic effect of emodin and cyclosporine A on rejective reaction against liver graft in rats

OBJECTIVE To investigate the mechanism of Emodin on the role of acute rejection in rat liver transplantation. METHOD Forty-eight pairs of orthotopic liver transplantation model were established with inbred rats which were randomly divided into 3 groups: Control group (BN --> BN), acute rejection group (Lewis --> BN) and emodin group (Lewis --> BN). Six recipients in each group were randomly collected and contents of TNF-alpha and IL-10 in the peripheral blood were detected with ELISA on Day 1, 3, 5 and 7 separately after transplantation and histopathological evaluation was made to detect the differences among groups after the livers were taken out on day 7. The other 10 in each group were protected to evaluate the animation and life time. RESULT The average meso-life time in emodin group (25.6 days) is significantly longer (P < 0.05) than acute rejection group (10.9 days). Compared with the acute rejection group, Emodin group shows up less rejection in the histopathological evaluation (P < 0.01), less TNF-alpha (P < 0.05) and a significant up-regulation of IL-10 in the peripheral blood (P < 0.05 after day 3). CONCLUSION Emodin can inhibit the acute rejection of liver transplantation in rats model effectively and it may play the role with reduction of TNF-alpha and upregulation of IL-10.

Effect of emodin on rejection of liver transplantation in rats

OBJECTIVE To evaluate the effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation (OLT) in rats. METHOD The LEW --> BN OLT models were established. A total of 24 rats were divided randomly and equally into 4 groups. Group A was treated with normal saline at dose of 0.5 mL x d(-1) intraperitoneally from 1st day to 8 th day after operation. Group B, CsA at dose of 10.0 mg x kg(-1) x d(-1). Group C, emodin at dose of 50.0 mg x kg(-1) x d(-1). Group D, CsA at dose of 10.0 mg x kg(-1) x d(-1) and emodin at dose of 50.0 mg x kg(-1) x d(-1). Fifteen days after operation, rejection active index (RAI) and hepatocellular apoptosis index (AI) was confirmed after observing the pathologic change of transplanted liver in recipients. RESULT Respectively, the RAI of group A, B, C, D was 7.67 +/- 0.98, 5.17 +/- 0.40, 5.83 +/- 0.75, 3.83 +/- 0.75 and the AI of group A, B, C, D was 35.83 +/- 2.320, 15.83 +/- 1.33, 16.50 +/- 2.35, 11.50 +/- 1.05. The RAI and AI of group B, C, D was significantly lower than group A (P < 0.01) and group D was significantly lower than group B, C too (P < 0.05). There was no significant distinction between group B and C in RAI and AI. CONCLUSION Emodin has the effect of reduce the hepatocellular apoptosis following OLT in rats and the effect can stronger by CsA.

Effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation in rats

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Papers

Effect of emodin in suppressing acute rejection following liver allograft transplantation in rats.

Synergistic effect of emodin and cyclosporine A on rejective reaction against liver graft in rats

Effect of emodin on rejection of liver transplantation in rats

Effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation in rats