Alkaloid Berberine Research Articles

Unified Synthesis of Polycyclic Alkaloids by Complementary Carbonyl Activation**

AbstractA complementary dual carbonyl activation strategy for the synthesis of polycyclic alkaloids has been developed. Successful applications include the synthesis of tetracyclic alkaloids harmalanine and harmalacinine, pentacyclic indoloquinolizidine alkaloid nortetoyobyrine, and octacyclic β‐carboline alkaloid peganumine A. The latter synthesis features a protecting‐group‐free assembly and an asymmetric disulfonimide‐catalyzed cyclization. Furthermore, formal syntheses of hirsutine, deplancheine, 10‐desbromoarborescidine A, and oxindole alkaloids rhynchophylline and isorhynchophylline have been achieved. Finally, a concise synthesis of berberine alkaloid ilicifoline B was completed.

Anticancer Potential of Natural Isoquinoline Alkaloid Berberine

Despite the availability of several therapeutic strategies and many drugs, the ability to cure most cancers remains a challenge. Natural products have been used for the treatment of numerous diseases, including cancer. The present review delineates various preclinical studies performed in vitro and in vivo that explore the anticancer potential of berberine, an isoquinoline alkaloid found in numerous plants as a secondary metabolite. Berberine can kill various types of human cancer cells in an optimal concentration- and duration-dependent manner and inhibit the growth of various types of cancers in animal models by elevating oxidative stress. In addition, berberine suppresses cell migration, invasion and epithelial-to-mesenchymal transition in different types of cancer cells. Mechanistically, berberine can induce cancer cell DNA fragmentation/apoptosis through extrinsic and intrinsic pathways, autophagy and necrosis. The cytotoxic effects of berberine in different types of cancer cells are mediated by its ability to induce oxidative stress and cell cycle arrest, and inhibit cell migration, invasion and epithelial-to-mesenchymal transition as well as matrix metalloproteinases through the modulation of Wnt and β-catenin signaling. A single clinical study has shown some promise in gastric cancer patients. Though berberine is a relatively safe compound, it should not be prescribed to pregnant or lactating women to avoid adverse effects on developing fetuses and neonates.

The Natural Alkaloid Berberine Can Reduce the Number of Pseudomonas aeruginosa Tolerant Cells.

The eradication of recurrent Pseudomonas aeruginosa (PA) lung infection in cystic fibrosis (CF) patients may be hampered by the development of persistent bacterial forms, which can tolerate antibiotics through efflux pump overexpression. After demonstrating the efflux pump inhibitory effect of the alkaloid berberine on the PA MexXY-OprM efflux pump, in this study, we tested its ability (80/320 μg/mL) to enhance tobramycin (20xMIC/1000xMIC) activity against PA planktonic/biofilm cultures. Preliminary investigations of the involvement of MexY in PA tolerance to tobramycin treatment, performed on the isogenic pair PA K767 (wild type)/K1525 (ΔmexY) growing in planktonic and biofilm cultures, demonstrated that the ΔmexY mutant K1525 produced a lower (100 and 10 000 times, respectively) amount of tolerant cells than that of the wild type. Next, we grew broth cultures of PAO1, PA14, and 20 PA clinical isolates (of which 13 were from CF patients) in the presence of 20xMIC tobramycin with and without berberine 80 μg/mL. Accordingly, most strains showed a greater (from 10- to 1000-fold) tolerance reduction in the presence of berberine. These findings highlight the involvement of the MexXY-OprM system in the tobramycin tolerance of PA and suggest that berberine may be used in new valuable therapeutic combinations to counteract persister survival.

Antimetastatic and Antitumor Activities of Orally Administered NAX014 Compound in a Murine Model of HER2-Positive Breast Cancer.

The natural isoquinoline alkaloid Berberine (BBR) has been shown to possess several therapeutic effects, including anticancer activity. Different BBR derivatives have been designed and synthesized in order to obtain new compounds with enhanced anticancer efficacy. We previously showed that intraperitoneal (IP) administration of the BBR-derived NAX014 compound was able to counteract HER-2 overexpressing mammary tumors onset and progression in transgenic mice. However, the IP administration was found to induce organ toxicity at doses higher than 2.5 mg/Kg. In this study, we evaluated the effect of intragastric (IG) administration of 20 mg/kg of NAX014 on both safety and anticancer efficacy in HER-2/neu transgenic mice. Furthermore, cancer cell dissemination and migration, tumor cell senescence and immunological changes were examined. Our results demonstrated that IG NAX014 administration delayed the onset of mammary tumors with no negative effects on health and survival. NAX014 reduced HER-2 overexpressing BC cells migration in vitro and the frequency of lung metastasis in HER-2/neu transgenic mice. A statistically significant increase of senescence-associated p16 expression was observed in tumors from NAX014-treated mice, and the induction of cell senescence was observed in HER-2 overexpressing BC cells after in vitro treatment with NAX014. Although NAX014 did not modulate the presence of tumor-infiltrating lymphocytes, the level of circulating TNF-α and VEGF was found to be reduced in NAX014-treated mice. The overall results address the NAX014 compound as potential tool for therapeutic strategies against HER-2 overexpressing breast cancer.

Benzylisoquinoline alkaloid content in goldenseal (Hydrastis canadensis L.) is influenced by phenological stage, reproductive status, and time-of-day

Goldenseal ( Hydrastis canadensis , Ranunculaceae/Hydrastidaceae) is a popular Appalachian medicinal forest plant whose roots and rhizomes are mostly collected from the wild for commerce. The benzylisoquinoline alkaloids (BIA) berberine, canadine, and hydrastine are believed to be primarily responsible for the bioactivity of goldenseal. To provide a consistent, quality-focused product to consumers, a better understanding of factors that influence major BIA levels is needed. We examined BIA content in relation to phenological stage, reproductive status (i.e., reproductive versus vegetative morphology), and time-of-day in wild and forest-farmed goldenseal collected in Pennsylvania, U.S.A. High performance liquid chromatography (HPLC) analysis revealed that phenological stage and reproductive status influences the BIA concentration in both dried belowground (roots, rhizomes) and aerial portions (leaves, stems). BIA levels were found to be higher in the belowground parts compared to aerial. Moreover, BIA concentrations peaked in both plant aerial and belowground portions at the flowering stage and in the belowground parts at dormancy, suggesting that an early season harvest of aerial tops could be explored in farmed populations in addition to traditional late season “root” harvests. Additionally, hydrastine and canadine levels were found to be greatest in aerial portions at 1600 h over a 24 -h range, which suggests late day as the best time for aerial harvests. Overall, these results provide guidance for optimizing alkaloid content in goldenseal harvests and contributes to the broader understanding of secondary metabolite in relation to plant phenological stage.

In vitro propagation and antioxidant potential of Berberis asiatica from Western Himalaya

An in vitro propagation protocol has been developed for Berberis asiatica, an important Himalayan medicinal shrub. Significantly higher in vitro seed germination (50%) was obtained in Murashige and Skoog (MS) medium with 1.0 µM 6-benzyladenine (BA). MS medium containing 1.0 µM BA and 0.1 µM 2,4-dichlorophenoxyacetic acid (2,4-D) yielded maximum callus induction percentage (100%) from in-vitro grown leaf explants. Maximum shoot proliferation (100%) was obtained when callus was transferred to MS medium containing 2.0 µM BA plus 0.5 µM IAA or 6.0 µM BA plus 0.5 µM NAA. The maximum rooting percentage (70%) and root number per shoot (2.36) were recorded in ½ MS containing 0.05 µM IAA. Rooted shoots when transferred to potting medium containing vermiculite, soil, and sand (1:1:1) resulted in 65% survival. The phytochemical analysis of leaf samples of tissue culture-raised plants showed significantly higher alkaloids (berberine and palmatine) content than the leaf samples collected from the wild (mother plant). A similar trend was also observed in studied antioxidant and antimutagenic activities. Therefore, micropropagation of B. asiatica can be promoted for harnessing its potential as a source of berberine and natural antioxidants. This may help to reduce the pressure on the natural populations of the species.

Establishing the metabolic network of isoquinoline alkaloids from the Macleaya genus

Metabolic networks can provide insight into the biosynthesis pathways of natural products present in plant-derived medicines. Here, we primarily established a highly efficient and targeted method for the systematic screening of isoquinoline alkaloids from the Macleaya genus. A total of 392 potential alkaloids were detected, 204 of which were further identified according to their tandem mass spectrometry (MS/MS) spectra and the characteristic fragmentation patterns of references. A metabolic network of isoquinoline alkaloids from the Macleaya genus was then constructed based on the structural relationships, metabolic level differences, and the isotopically labeled [ring-13C6]-tyrosine feeding experiments. New biosynthesis pathways for well-known alkaloids (berberine, sanguinarine, and chelerythrine) in the Macleaya genus were proposed on the basis of the established metabolic network. This work marks the first comprehensive study of the metabolic network of isoquinoline alkaloids in the Macleaya genus and provides a template for constructing the metabolic networks of other plant-derived medicines.

Influence of Postharvest Drying Temperatures on Alkaloid Levels in Goldenseal (Hydrastis canadensis L.)

Goldenseal (Hydrastis canadensis L.) is a medicinal forest herb native to Appalachia. Its roots and rhizomes are used as an antimicrobial and for the treatment of intestinal ailments. Three alkaloids–berberine, hydrastine, and canadine–are recognized as the major bioactive constituents in goldenseal. One important postharvest processing step for goldenseal is drying; however, it is not known how drying temperature influences the concentrations of these alkaloids. In this study, pre-emergent (dormant) goldenseal samples were freeze-dried or air-dried at six different temperatures (26.7 to 54.4 °C) to determine the relationship between drying temperature and alkaloid content in the rhizome and roots. High performance liquid chromatography analysis showed that berberine and hydrastine levels were unaffected by drying temperature, while canadine levels decreased as temperature increased (0.55% w/w on average when samples were freeze-dried, down to 0.27% w/w on average when dried at 54.4 °C). While canadine is the least abundant alkaloid of the three, it is known to have key antibacterial properties. Developing a more standardized drying protocol for goldenseal could lead to a more predictable phytochemical profile.

Identification of the Myogenetic Oligodeoxynucleotides (myoDNs) That Promote Differentiation of Skeletal Muscle Myoblasts by Targeting Nucleolin.

Herein we report that the 18-base telomeric oligodeoxynucleotides (ODNs) designed from the Lactobacillus rhamnosus GG genome promote differentiation of skeletal muscle myoblasts which are myogenic precursor cells. We termed these myogenetic ODNs (myoDNs). The activity of one of the myoDNs, iSN04, was independent of Toll-like receptors, but dependent on its conformational state. Molecular simulation and iSN04 mutants revealed stacking of the 13–15th guanines as a core structure for iSN04. The alkaloid berberine bound to the guanine stack and enhanced iSN04 activity, probably by stabilizing and optimizing iSN04 conformation. We further identified nucleolin as an iSN04-binding protein. Results showed that iSN04 antagonizes nucleolin, increases the levels of p53 protein translationally suppressed by nucleolin, and eventually induces myotube formation by modulating the expression of genes involved in myogenic differentiation and cell cycle arrest. This study shows that bacterial-derived myoDNs serve as aptamers and are potential nucleic acid drugs directly targeting myoblasts.

Yellow Medicine of Nature- The future Chartbuster Protoberberine Antivirals

Emerging viral diseases are one of the principal threat towards the plants, animals and humans. Viruses are fast evolving, resulting in reduced effectiveness of existing drugs and vaccines. At this juncture, the importance of traditional medicine, as well as medicinal plant active principles, occupies central attention of researchers across the world. Protoberberine alkaloids, an essential group of isoquinoline family of alkaloids, exhibit properties were affecting the life cycle of DNA and RNA viruses. However, from this protoberberine group, only berberine alkaloid has been studied in detail for its mechanism of action. Berberine is useful both in the case of enveloped and non-enveloped viruses. Berberine inhibits viral life cycle by modulating NF-kB signalling, targeting viral glycoproteins and downregulation of MEK-ERK signalling. Apart from this, berberine also inhibits ACE. All protoberberine alkaloids share a characteristic protoberberine skeleton. The protoberberine containing botanicals also exhibited antiviral properties. Therefore protoberberine alkaloids and protoberberine containing botanicals are interesting to experiment in detail for their antiviral properties and mechanism of action in emerging viral diseases of plants, animals and humans.

Stereoselective Synthesis of Diastereomeric Berberine Alkaloids, O-Methylcorytenchirine and Coralydine

Stereoselective Synthesis of Diastereomeric Berberine Alkaloids, O-Methylcorytenchirine and Coralydine

Evaluation of silymarin and berberine efficiencies in the self-emulsifying drug delivery systemin paracetamol-induced experimental toxic liver injury

The hepatoprotective properties of the silymarin and the plant alkaloid berberine combinationin experimental paracetamol-inducedliver damage were studied. Silymarin was obtained from milk thistle seeds. The conditions for extraction of flavonolignans (silymarin) were optimized. 70 % ethyl alcohol, ethyl acetate and water were used as extractants. It was shown that the optimal conditions for the extraction of flavonolignans in order to obtain the maximum yield of flavonolignans were alcohol extraction in a Soxhlet apparatus. The experiment showed that the combined of silymarin and berberine was greater than their individual actions, which most effectively permitted stabilization of hepatocyte membranes and prevented altering their integrity in paracetamol-induced toxic liver damage. The self-emulsifying system with silymarin and berberine to a greater extent a significant extent prevented dystrophic changes in hepatocytes and necrosis in liver tissue, reduced hyperfermentemia in rat blood serum, prevented disturbance in the activity of thioredoxin reductase and enzymes of the glutathione antioxidant system and there by more effectively prevented hepatocyte functional impairment.

In vitro and in silico studies of the larvicidal and anticholinesterase activities of berberine and piperine alkaloids on Rhipicephalus microplus

Rhipicephalus microplus is responsible for high economic losses in livestock and its control has become difficult due to the establishment of tick populations resistant to commercial acaricides. This study aimed to evaluate the in vitro larvicidal effect of the alkaloids berberine and piperine, and also to investigate their inhibitory mechanisms against the acetylcholinesterase enzyme. The effects of the alkaloids on larvae were observed through the immersion test at the following concentrations: 1.5; 3; 6; 12; 16 and 24 mM. Berberine and piperine presented larvicidal activity greater than 95 %, not differing from 100 % for the positive fipronil control (p > 0.05). Of the two alkaloids, piperine had a lower effective concentration (EC), with an EC50 of 6.04 mM. The acetylcholinesterase enzyme used in the study was obtained from R. microplus larvae (RmAChE) and the anticholinesterase activity was determined spectrophotometrically. The highest anticholinesterase activity, measured as inhibition concentration (IC), was observed for berberine (IC50 = 88.13 μM), while piperine showed lower activity (IC50 > 200 μM). Docking studies in RmAChE, followed by 10 ns molecular dynamics simulation, suggest that berberine stabilizes the RmAChE at lower Root-Mean-Square Deviation (RMSD) than Apo protein. Few hydrogen-bond interactions between berberine and RmAChE residues were balanced by hydrophobic and π-type interactions. Berberine fills preferentially the peripheral anionic site (PAS), which correlates with its non-competitive mechanism. These results suggest that berberine and piperine alkaloids have an in vitro acaricidal action on R. microplus larvae, and the likely mechanism of action of berberine is related to RmAChE inhibition when accessing the PAS residues. These findings could help the study of new natural products that could inhibit RmAChE and aid in the development of new acaricides.

RETRACTED ARTICLE: Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma

BackgroundThe ability to treat glioblastoma (GBM) using the chemotherapeutic agent temozolomide (TMZ) has been hampered by the development of therapeutic resistance. In this study, we assessed the ability of the isoquinoline alkaloid berberine to alter GBM TMZ resistance using two different TMZ-resistant cell lines to mimic a physiologically relevant GBM experimental system.MethodsBy treating these resistant cell lines with berberine followed by TMZ, we were able to assess the chemosensitivity of these cells and their parental strains, based on their performance in the MTT and colony formation assays, as well as on the degree of detectable apoptosis that was detected in the strains. Furthermore, we used Western blotting to assess autophagic responses in these cell lines, and we extended this work into a xenograft mouse model to assess the in vivo efficacy of berberine.ResultsThrough these experiments, our findings indicated that berberine enhanced autophagy and apoptosis in TMZ-resistant cells upon TMZ treatment in a manner that was linked with ERK1/2 signaling. Similarly, when used in vivo, berberine increased GBM sensitivity to TMZ through ERK1/2 signaling pathways.ConclusionsThese findings demonstrate that berberine is an effective method of increasing the sensitization of GBM cells to TMZ treatment in a manner that is dependent upon the ERK1/2-mediated induction of autophagy, thus making berberine a potentially viable therapeutic agent for GBM treatment.

Development of Thermoreversible Dental Gel with Berberine

Introduction. Dental gel is one of the modern dosage forms with optimal biopharmaceutical properties for the treatment and prevention of oral diseases An isoquinoline alkaloid berberine is the promising active substance with antibacterial and anti-inflammatory effect, capable of forming stable dispersed systems with gel-forming components. It is noteworthy that, despite the pronounced antimicrobial activity of the alkaloid berberine, there is currently no dental dosage form with this component on the pharmaceutical market, and therefore research in this direction is of great interest.Aim. Selection of the optimal technology for obtaining dental gel with berberine for the treatment of oral diseases.Materials and methods. Berberine bisulfate (manufactured by CJSC «Vifitech», Obolensk, Moscow region, RF), poloxamers P407 and P338 (EP, USP/N; BASF, Germany), propylene glycol (USP; BASF, Germany), sodium chloride (Sigma-Aldrich, Germany, Cat. No. S9888), mucin type II from a pig stomach (Sigma-Aldrich, Germany, Cat. No. M2378). In the development of the composition and technology for the preparation of gels, a magnetic stirrer with a temperature control function (C-MAG HS 7 from IKA, Germany) was used. Gels were prepared by the «hot method» and «cold method».Results and discussion. The production of the gel by the «hot method» provided a uniform dosage form. The obtained pH value is within the range of optimal diapason. Measurement of the specific peel force of the model gel sample showed pronounced mucoadhesive properties, which indicates that there is no need to adjust this parameter by introducing additional components into the formulation. The spectroscopic method is applicable for the analysis of berberine gel. It has been found that a significant dilution of the reference substance sample is required to develop an identification procedure.Conclusion. The production of a sample of the dosage form by the «hot method» is optimal, which is probably due to the effect of solubilization and better distribution of the active substance in the base.

Study of alkaloid berberine and its interaction with the human telomeric i-motif DNA structure

The alkaloid berberine presents many biological activities related to its potential to bind DNA structures, such as duplex or G-quadruplex. Recently, it has been proposed that berberine may interact with i-motif structures formed from the folding of cytosine-rich sequences. In the present work, the interaction of this alkaloid with the i-motif formed by the human telomere cytosine-rich sequence, as well as with several positive and negative controls, has been studied. Molecular fluorescence and circular dichroism spectroscopies, as well as nuclear magnetic resonance spectrometry and competitive dialysis, have been used with this purpose. The results shown here reveal that the interaction of berberine with this i-motif is weak, mostly electrostatics in nature and takes place with bases not involved in C·C+ base pairs. Moreover, this ligand is not selective for i-motif structures, as binds equally to both, folded structure, and unfolded strand, without producing any stabilization of the i-motif. As a conclusion, the development of analytical methods based on the interaction of fluorescent ligands, such as berberine, with i-motif structures should consider the thermodynamic aspects related with the interaction, as well as the selectivity of the proposed ligands with different DNA structures, including unfolded strands.

Exposure to the natural alkaloid Berberine affects cardiovascular system morphogenesis and functionality during zebrafish development

The plant-derived natural alkaloid berberine displays therapeutic potential to treat several pathological conditions, including dyslipidemias, diabetes and cardiovascular disorders. However, data on berberine effects during embryonic development are scarce and in part controversial. In this study, using zebrafish embryos as vertebrate experimental model, we address the effects of berberine treatment on cardiovascular system development and functionality. Starting from the observation that berberine induces developmental toxicity and pericardial edema in a time- and concentration-dependent manner, we found that treated embryos display cardiac looping defects and, at later stages, present an abnormal heart characterized by a stretched morphology and atrial endocardial/myocardial detachment. Furthermore, berberine affected cardiac functionality of the embryos, promoting bradycardia and reducing the cardiac output, the atrial shortening fraction percentage and the atrial stroke volume. We also found that, during development, berberine interferes with the angiogenic process, without altering vascular permeability. These alterations are associated with increased levels of vascular endothelial growth factor aa (vegfaa) mRNA, suggesting an important role for Vegfaa as mediator of berberine-induced cardiovascular defects. Altogether, these data indicate that berberine treatment during vertebrate development leads to an impairment of cardiovascular system morphogenesis and functionality, suggesting a note of caution in its use during pregnancy and lactation.

Enhanced in vitro antimicrobial activity of amphotericin B with berberine against dual-species biofilms of Candida albicans and Staphylococcus aureus.

Multi-species biofilms formed by fungi and bacteria are clinically common and confer the commensal micro-organisms with protection against antimicrobial therapies. Previously, the plant alkaloid berberine was reported to show antimicrobial efficacy to eliminate bacterial and fungal biofilms. In this study, the combination of berberine and amphotericin B, an antifungal agent, was evaluated against dual-species Candida albicans/Staphylococcus aureus biofilms. Combinatorial treatment by berberine and amphotericin B significantly reduced the biomass and viability of residing species in biofilms. Moreover, morphological examination revealed hyphal filamentation of C. albicans and coadhesion between C. albicans/S. aureus were considerably impaired by the treatment. These effects coincided with the reduced expression of cell surface components and quorum-sensing-related genes in both C. albicans and S. aureus. Additionally, in C. albicans, the core transcription factors for controlling biofilm formation together with a crucial component of dual-species biofilms were also downregulated. These results demonstrated synergistic effects of berberine and amphotericin B against C. albicans/S. aureus dual-species biofilms. This study confirms the potential of berberine and amphotericin B for treating the C. albicans/S. aureus biofilms related infections and reveals molecular basis for the efficacy of combinatorial treatment.

Berberine affects mitochondrial activity and cell growth of leukemic cells from chronic lymphocytic leukemia patients

B-cell chronic lymphocytic leukemia (CLL) results from accumulation of leukemic cells that are subject to iterative re-activation cycles and clonal expansion in lymphoid tissues. The effects of the well-tolerated alkaloid Berberine (BRB), used for treating metabolic disorders, were studied on ex-vivo leukemic cells activated in vitro by microenvironment stimuli. BRB decreased expression of survival/proliferation-associated molecules (e.g. Mcl-1/Bcl-xL) and inhibited stimulation-induced cell cycle entry, irrespective of TP53 alterations or chromosomal abnormalities. CLL cells rely on oxidative phosphorylation for their bioenergetics, particularly during the activation process. In this context, BRB triggered mitochondrial dysfunction and aberrant cellular energetic metabolism. Decreased ATP production and NADH recycling, associated with mitochondrial uncoupling, were not compensated by increased lactic fermentation. Antioxidant defenses were affected and could not correct the altered intracellular redox homeostasis. The data thus indicated that the cytotoxic/cytostatic action of BRB at 10–30 μM might be mediated, at least in part, by BRB-induced impairment of oxidative phosphorylation and the associated increment of oxidative damage, with consequent inhibition of cell activation and eventual cell death. Bioenergetics and cell survival were instead unaffected in normal B lymphocytes at the same BRB concentrations. Interestingly, BRB lowered the apoptotic threshold of ABT-199/Venetoclax, a promising BH3-mimetic whose cytotoxic activity is counteracted by high Mcl-1/Bcl-xL expression and increased mitochondrial oxidative phosphorylation. Our results indicate that, while CLL cells are in the process of building their survival and cycling armamentarium, the presence of BRB affects this process.

Comparative Effects of Yellow Root (Arcangelisia flava (L.) Merr.) Decoctions with Water and Brackish Water on Kidneys and Uterus in Wistar Rats

Yellow root (Arcangelisia flava (L.) Merr.) is a medicinal plant used traditionally in Borneo, Indonesia, for several diseases. Nevertheless, it contains berberine alkaloids that are considered harmful. Empirically, based on local wisdom people do not boil yellow roots with water but with brackish water. This study aimed to determine the effects of yellow root decoctions made using water and brackish water on blood biochemical and histopathological profile of kidneys and uterus in Wistar rats after subchronic treatment. Overall, 70 Wistar female rats were divided into seven groups of which three groups were given yellow root water decoctions and three groups were given yellow root brackish water decoctions with doses equivalent to 1.25 g/kg BW, 2.5 g/kg BW and 5 g/kg BW of dried yellow root, whereas the control group was only given Aquadest. After 28 days of treatments, blood samples were obtained for biochemical examination followed by a surgical examination to observe the histological features of the organs. The results revealed significant differences in the blood urea nitrogen (BUN) levels between group that was given water decoction of the yellow root and the control group. On the other hand, the groups that were given brackish water decoction revealed no significant changes, except at the highest dose. Furthermore, histopathological features of rats treated using all doses of the yellow root water decoctions revealed organ damage compared with the normal group, manifested as hemorrhage, degeneration, and necrosis of the kidneys, as well as epithelial damage and inflammatory infiltration of the uterus.