Rat Pica Model Research Articles

Xiao-Ban-Xia Decoction Alleviates Chemotherapy-Induced Nausea and Vomiting by Inhibiting Ferroptosis via Activation of The Nrf2/SLC7A11/GPX4 Pathway.

Chemotherapy-induced nausea and vomiting (CINV) represents the common gastrointestinal side effect for cancer patients. Xiao-Ban-Xia decoction (XBXD), a classical anti-emetic traditional Chinese medicine formula, is frequently used for the clinical treatment of CINV. This study used a cisplatin-induced rat pica model to explore whether the anti-emetic mechanism of XBXD in treating CINV is related to ferroptosis. The inflammatory damage of the gastrointestinal tract is evaluated by HE staining and ELISA. The degree of ferroptosis are validated by the iron deposition, the levels of ROS, MDA, and GSH, and the ultrastructure of mitochondria in the gastric antrum and ileum. The potential ferroptosis-related targets of XBXD against CINV are screened by network pharmacology and further assessed by Western blot. XBXD significantly decreased the kaolin consumption in rats, and improved the inflammatory pathological damage, with decreased levels of HMGB1, IL-1β, and TNF-α. Furthermore, XBXD significantly suppressed ferroptosis, as indicated by the improvement of iron deposition, mitochondrial abnormalities, and oxidative stress. The network pharmacology and Western blot results indicated that XBXD activated the Nrf2/SLC7A11/GPX4 signaling pathway. This study proved that XBXD activates the Nrf2/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis, which represents a critical anti-emetic mechanism of XBXD in combatting CINV.

Role of Sapindus emarginatus Pericarp Extract in Gut Serotonin Level and its Emetic Activity in Animal Models

Background: Emesis is a complex and distressing protective mechanism that helps to remove toxic substances from the stomach and prevent further ingestion. The emetics and cathartics are predominantly used for accidental and intentional ingestion of poisons or toxins. The availability and usage of emetics in humans are limited because of their side effects. Therefore, to treat poisoned people, we need effective medications. Sapindus emarginatus Vahl., often called soapnut, is a member of the Sapindaceae family. They have historically been used as emetic, antipruritic, laxative, antifertility, and anti-inflammatory medicines. Objective: This study aims to assess the gut serotonin level and emetic effect of Sapindus emarginatus hydroethanolic pericarp extract (HESE) by using animal models. Methods: Gravimetric analysis was used to determine the HESE's saponin content. The emetic effect of the HESE at a dose of 250, 500, 1000, and 2000 mg/kg was evaluated by copper sulfateinduced emesis in the chick model and cisplatin-induced emesis in the rat-pica model. The serotonin level in rat intestinal mucosa was measured by spectrofluorimetry. Results: HESE was estimated to contain 11.92% saponin. The extract at high doses of 1000 and 2000 mg/kg showed emetic activity evidenced by increased frequency of retching in chick, increased kaolin intake, and anorexia in the rat-pica model. The extract showed a significant increase in serotonin levels in the proximal part of the small intestine in comparison with normal animals. Conclusion: According to the results of the current investigation, which employed various animal models, the HESE demonstrated appreciable emetic activity. The extract at a high dose showed a significant emetic effect due to increased serotonin levels in the gut. The HESE was discovered to be a strong contender for the treatment of poisoned patients. More research are required to validate their adverse effects of frequent usage.

Xiao-Ban-Xia decoction mitigates cisplatin-induced emesis via restoring PINK1/Parkin mediated mitophagy deficiency in a rat pica model

Ethnopharmacological relevanceAs a traditional Chinese anti-emetic formula, Xiao-Ban-Xia decoction (XBXD) was recorded in Golden Chamber, and has promising anti-emetic effect on chemotherapy-induced nausea and vomiting (CINV). Aim of the studyThis study aimed to determine whether the underlying mechanism of XBXD against CINV is correlated to the restoration of cisplatin-induced PINK1/Parkin mediated mitophagy deficiency and mitigation of gastrointestinal inflammation. Materials and methodsThe rat pica model was established by intraperitoneal injection of cisplatin 6 mg/kg. The daily kaolin consumption, food intake and body weight were recorded every 24 h. The pathological damage of gastric antrum and ileum were observed by hematoxylin-eosin staining. The levels of serum reactive oxygen species (ROS), interleukin-1β (IL-1β) and interleukin-1β (IL-18) were detected by ELISA. The expression of microtubule-associated protein 1 light chain 3 (LC3) in gastric antrum and ileum was detected by Immunofluorescence staining. The levels of LC3II, P62/SQSTM1, PTEN-induced putative protein kinases (PINK1), E3 ubiquitin ligase (Parkin), AMP-dependent protein kinases (AMPK), phosphorylated AMPK (p-AMPK), nuclear factor erythroid 2-related factor (Nrf2) and kelch like ECH Associated Protein 1 (Keap1) in gastric antrum and ileum were assayed by western blotting. ResultsAt 24 h and 72 h following cisplatin challenge, XBXD inhibited cisplatin-induced elevation of kaolin consumption, and improved the daily food intake and body weight loss in rats. Cisplatin-induced gastrointestinal histopathological damages were alleviated, and serum levels of ROS, IL-1β and IL-18 increases were mitigated following XBXD treatments. In gastric antrum and ileum, XBXD activated AMPK-Nrf2 signaling pathway and restored cisplatin-induced PINK1/Parkin mediated mitophagy deficiency. ConclusionsXBXD significantly ameliorated CINV in a cisplatin-induced rat pica model. The underlying anti-emetic mechanism of XBXD might be related to the activation of AMPK-Nrf2 signaling pathway and the restoration of cisplatin-induced PINK1/Parkin-mediated mitophagy deficiency in the gastrointestinal tract.

Liujunanwei decoction attenuates cisplatin-induced nausea and vomiting in a Rat-Pica model partially mediated by modulating the gut micsrobiome.

Studies show that traditional Chinese medicine (TCM), such as Liujunanwei (LJAW) decoction, can play important roles in alleviating side effects of chemotherapy. The purpose of this study was to understand how LJAW can counter chemotherapy-induced emesis via alteration of gut microbiota. We evaluated the effect of LJAW on cisplatin (DDP)-induced nausea and vomiting using a rat-pica model. Rats react to emetic-producing stimuli with increased kaolin consumption, a phenomenon called pica. The rats were injected with cisplatin and then randomly assigned to the control (DDP), Ondansetron or LJAW. The intake of kaolin and chow diet as well as body weights were recorded every 24 hours. Fecal samples were collected prior to, after three and seven days of treatment. The expression of proteins was measured by western blot. The concentration of cytokines and serotonin was evaluated using ELISA assay kits. Kaolin consumption in rats induced by cisplatin was reduced by 16.5%, 22.5%, and 30.1% in the LJAW group compared to the DDP group at 24 hours, 48 hours and 72 hours, respectively (p>0.05). LJAW significantly increased the food intake of the rats (13.94 ± 4.73 g) during the first 24 hours as opposed to the DDP (9.23 ± 3.77 g) (p<0.05). 16S rRNA gene sequencing showed the abundance of Bacteroidetes increased in cisplatin treated rats. In addition, cisplatin injection caused an enrichment of Escherichia-Shigella and Enterococcus at the genus level. While, enrichment of Blautia and Lactobacillus was presented in LJAW treated rats. Serotonin decreased in LJAW treated intestine and medulla oblongata tissues. Further, the protein expression of tryptophan hydroxylase 1 (TPH1) a rate limiting enzyme of serotonin was inhibited in LJAW treated rat’s jejunum compared with cisplatin only treated rats. In addition, LJAW downregulated chemotherapy induced elevated inflammation. The results of this study indicated that LJAW is capable of decreasing cisplatin-induced kaolin intake in rat-nausea model (pica), which might be mediated through gut microbiome-induced anti-inflammation and anti-serotonin synthesis functions.

Forsythiae Fructus aqueous extract attenuates cisplatin-induced kaolin consumption (pica) by inhibiting NLRP3 inflammasome activation in rats.

The present study was conducted to evaluate the effect of Forsythiae Fructus aqueous extract (FAE) against cisplatin-induced emesis and to explore the antiemetic mechanism of FAE by focusing on NLRP3 inflammasome activation in a rat pica model. Our results showed that FAE significantly ameliorated cisplatin-induced acute and delayed pica in rats. Moreover, FAE improved the gastrointestinal histopathological injury and reduced the levels of serum ROS, IL-1β, and IL-18 in cisplatin-treated rats. In addition, the expressions of NLRP3, ASC, caspase-1, and IL-1β and the colocalization of the NLRP3 with ASC or caspase-1 in rat gastric antrum and ileum were also suppressed by FAE. Taken together, our findings indicate that FAE has a therapeutic effect against CINV, which may be related to its inhibition of the activation of NLRP3 inflammasome.

Crucial involvement of catecholamine neurotransmission in postoperative nausea and vomiting: Whole-transcriptome profiling in the rat nucleus of the solitary tract.

The genetic mechanisms of postoperative nausea and vomiting (PONV) and the involvement of the catecholamine system in the brain have not been elucidated. Eating kaolin clay as a type of pica has been examined as an alternative behavior to emesis. Here, we evaluated changes in whole-transcriptome analysis in the nucleus of the solitary tract (NTS) in a rat pica model as a surrogate behavior of PONV to elucidate the molecular genetic mechanisms of the development of PONV and the involvement of the catecholamine system in the NTS. First, kaolin pica behaviors were investigated in 71 female Wistar rats following isoflurane anesthesia, surgical insult or morphine administration. Multiple linear regression analysis showed that 3mg/kg morphine increased kaolin intake by 2.8g (P=0.0002). Next, total RNA and protein were extracted from the dissected NTS, and whole-transcriptome sequencing (RNA-seq) was performed to identify PONV-associated genes and to verify the involvement of the catecholamine system. The gene expression levels of tyrosine hydroxylase and dopamine beta-hydroxylase in the catecholamine biosynthesis pathway decreased significantly in the PONV model. Release of noradrenaline, a catecholamine pathway end product, may have increased at the synaptic terminal of the NTS neuron after pica behavior. Systematic administration of α2 adrenergic receptor agonists after surgery reduced kaolin intake from 3.2g (control) to 1.0g (P=0.0014). These results indicated that catecholamine neurotransmission was involved in the development of PONV in the NTS.

Involvement of 5-Serotonin and Substance p Pathways in Dichroa Alkali Salt-Induced Acute Pica in Rats.

Dichroa alkali salt (DAS) is the active ingredient of Changshan, a traditional Chinese antimalarial medicine. However, owing to its vomiting side effects, its clinical use is limited. Recently, DAS-induced vomiting has attracted broad attention; however, the mechanisms involved have not yet been elucidated. The present study aimed to explore DAS induced vomiting and decipher the potential role of the 5-serotonin (5-HT) and substance p (SP) signaling pathways. We used a combination of approaches in the context of a rat pica model, such as immunoblot analysis, HPLC-ECD, ELISA, quantitative real-time PCR, pharmacological inhibition, and immunohistochemistry assays. We demonstrated that DAS contributed to Changshan-induced vomiting via the activation of the 5-HT and SP signaling pathways. DAS could induce a dose-dependent kaolin intake in the rat pica model. Moreover, DAS caused a similar profile as Cisplatin (DDP): “low-dose double-peak, high-dose single-peak pica phenomenon”. Interestingly, treatment with DAS stimulated the peripheral ileum and central medulla oblongata and augmented the release of 5-HT, SP, and preprotachykinin-A and the expression of 5-HT3 and NK1 receptors in the two issues in acute phase. Additionally, the 5-HT3 and NK1 receptor antagonists effectively alleviated DAS-induced kaolin intake and significantly reduced DAS-induced 5-HT and SP levels in the two issues in acute phase. Similar responses were not observed in the context of dopamine receptor inhibition. This study innovatively revealed that the 5-HT and SP-mediated vomiting network plays an important role in DAS-induced acute vomiting; of note, ondansetron, and aprepitant can effectively antagonize DAS-induced vomiting. Our results suggest a potential therapeutic strategy (based on drugs approved for human use) to prevent the DAS-associated adverse reactions.

Feasibility study of morphine-induced rat pica model by tail vein injection to replace vomiting model

Objective： To explore the feasibility of the morphine-induced rat pica model by tail vein injection to replace the vomiting model，and the effective dose of morphine with less severe complications when the model was developed.Methods： Fifty SD rats were randomly divided into the blank control group and the M1，M2，M3 and M4 groups，each consisting of 10 animals. The rats in the blank control group were injected with 10 ml/kg normal saline（NS） via tail vein，while the animals in the M1，M2，M3 and M4 groups were injected with morphine hydrochloride injection at a dosage of 5，10，20 and 30 mg/kg via tail vein.Heart rate，blood oxygen saturation and activities of the animals were closely observed and recorded at 5，10 and 15 minutes after medication.Then，changes in the intake of kaolin，feed and water of the rats in each group were recorded and compared between the groups for 4 successive days after medication.Results： The blood oxygen saturation in the morphine treatment groups all reduced significantly，and statistical significance could be seen，when it was compared with that of the blank control group（P&lt;0.05）.On the first day after medication，the intake of kaolin in the M3 and M4 groups increased significantly，as compared with that of the blank control group（P&lt;0.05）.On the third day after medication，the intake of kaolin in the M1 group significantly increased，as compared with that of the blank control group（P&lt;0.05）.Conclusion： The rat pica model was established by tail vein injection of morphine，which could be used to replace the vomiting model.The effective dose of morphine was 20 mg/kg with less severe complications.

RNA-Seq reveals inflammatory mechanisms of Xiao-Ban-Xia-Tang decoction to ameliorate cisplatin-induced emesis in a rat pica model

ObjectivesXiao-Ban-Xia-Tang decoction (XBXT), an antiemetic formula in traditional Chinese medicine, has been proved to be a potential treatment for chemotherapy-induced nausea and vomiting (CINV), but the underlying mechanisms are not adequately understood. This study aimed to investigate changes in the ileum transcriptome after cisplatin and XBXT treatment and to reveal whether the antiemetic mechanisms of XBXT are related to its anti-inflammatory effect. MethodsThe pica model was established by a single intraperitoneal injection of 6 mg/kg cisplatin in Wistar rats. Tissues from the gastric antrum and ileum were stained with hematoxylin-eosin to observe gastrointestinal tract pathological changes. Based on the differentially expressed genes (DEGs) which were altered by cisplatin and reversed by XBXT, the transcriptome data of rat ileum were analyzed by GO, KEGG, and PPI analyses. Several inflammatory DEGs were validated by RT-PCR. ResultsXBXT could reduce kaolin intake up to 72 h after modeling and alleviate the inflammatory damage of gastric antrum and ileum induced by cisplatin. According to the transcriptome profile, there were 75 DEGs down-regulated by cisplatin and up-regulated by XBXT and 343 DEGs up-regulated by cisplatin and down-regulated by XBXT. XBXT could blunt the overexpression of tryptophan hydroxylase 1 (the rate-limiting enzyme of serotonin synthesis) in ileum. Enrichment analysis showed that inhibiting overexpression of several conventional inflammation pathways and pro-inflammation cytokines were related to the antiemetic effectiveness of XBXT. ConclusionsThis study implies that inhibiting inflammatory signaling pathways and synthesis of serotonin might be potential mechanisms of XBXT’s antiemetic effect against CINV.

The Antiemetic Effect of Xiao‐Ban‐Xia‐Tang Formula against Cisplatin‐Induced Emesis is Mediated through Inhibition of NLRP3 Inflammasome Activation in a Rat Pica Model

Xiao-Ban-Xia-Tang (XBXT), a traditional Chinese medicine formula, has been used for the treatment of emesis for nearly 2000 years, but its underlying mechanism is not yet fully clarified. The purpose of this study is to reveal the antiemetic mechanisms of XBXT by focusing on the NLRP3 inflammasome pathway in a chemotherapy-induced rat pica model. The pica model was generated by a single intraperitoneal injection of cisplatin in this study. Consumption of kaolin (a type of clay) and food and body weight were recorded every 24 hours. Cisplatin-induced increase in kaolin consumption (pica) was used to quantify chemotherapy-induced nausea and vomiting (CINV). Tissue from the ileum and antrum was stained with hematoxylin eosin (HE) to observe pathological changes. The levels of reactive oxygen species (ROS) and inflammatory cytokines, including IL-1β and IL-18 in serum, were detected by ELISA. In addition, changes in the NLRP3 inflammasome activation in the ileum and antrum were investigated using western blot and immunofluorescence microscopy. The results showed that oral administration of XBXT and ondansetron inhibited acute and delayed pica and significantly protected against the gastrointestinal pathological injury induced by cisplatin. The levels of ROS, IL-1β, and IL-18 in the serum of cisplatin-treated rats were also remarkably decreased by XBXT and ondansetron. Moreover, we found that XBXT can inhibit cisplatin-induced NLRP3 inflammasome activation. The present study indicates that the inhibition of the NLRP3 inflammasome activation might be one of the potential mechanisms for the therapeutic effects of XBXT against CINV.

The Anti-emetic Effect of Banhasasim-tang Intravenous Herbal Acupuncture in MTX-induced Rat-Pica Model

The Anti-emetic Effect of Banhasasim-tang Intravenous Herbal Acupuncture in MTX-induced Rat-Pica Model

Ginsenoside rich fraction of Panax ginseng C.A. Meyer improve feeding behavior following radiation-induced pica in rats

Panax ginseng is an indigenous medicinal herb and has traditionally been used among Asian population for relief of many human ailments. We investigated the prophylactic role of Korean P. ginseng extract (KG) against X-ray irradiation-induced emesis in an acute rat pica model. Rats were treated with KG (12.5, 25, 50mg/kg orally at −48, −24 and 0h) prior to X-ray irradiation (6Gy), and intake of kaolin and normal food and body weight changes examined as an index of the acute emetic stimulus. Levels of serotonin in small intestine tissue were assessed and histopathology of gastric tissue, small intestine and colon examined specific staining. Pre-treatment with KG (12.5 and 25mg/kg) reduced X-ray irradiation-induced kaolin intake at 24h. Normal food intake was improved in rats treated with 25mg/kg KG. The anti-emetic effect of KG was further confirmed on the basis of serotonin release, histopathological findings. Our findings collectively indicate that KG protects against X-ray irradiation-induced acute pica to a moderate extent, leading to improved feeding behavior in rats.

Effects of Korean ginseng root extract on cisplatin-induced emesis in a rat-pica model

In the present study, we investigate the effect of Korean ginseng root extract (KG) on cisplatin-induced pica in a rat model. Rats were treated with KG before (25, 50, and 100mg/kg) or after (12.5, 25, and 50mg/kg) a single intraperitoneal injection of cisplatin (7 and 6mg/kg, respectively). We examined intake of kaolin and normal food as an indicator of the emetic stimulus every 24h for 120h. Changes in body weight, haematology and histopathology were additionally assessed. Pre-treatment with KG (25 and 50mg/kg) significantly attenuated cisplatin-induced kaolin intake (24, 48, and 72h) and markedly improved intake of normal food by rats at 48, 72, 96, and 120h. Cisplatin-induced kaolin intake was markedly decreased upon post-treatment of rats with KG (12.5, 25, and 50mg/kg) at 24h. Notably, post-treatment with the lowest KG dose resulted in a significant anti-pica effect and improved food intake until 72h. The magnitude of body weight reduction was significantly diminished in rats pre-treated/post-treated with 25, 50, and 12.5mg/kg KG. The anti-pica effects of KG were further confirmed with haematological and histopathological findings. Our findings collectively indicate that KG improves the resistance of rats against emesis.

Scutellaria baicalensis and a constituent flavonoid, baicalein, attenuate ritonavir-induced gastrointestinal side-effects.

Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans. The effects of herb administration on gastric emptying in rats were also measured. Ritonavir treatment resulted in increased kaolin intake or severe pica, the intensity of which was reduced significantly with S. baicalensis administration (1 mg kg(-1); P<0.05). High-performance liquid chromatography analysis of S. baicalensis showed the presence of an extremely potent flavonoid constituent, baicalein. The study aimed to determine if baicalein contributed to the anti-pica effect of the extract. It was observed that baicalein dose-dependently decreased pica in ritonavir-treated rats (P<0.001). In addition to inducing pica, ritonavir also significantly delayed gastric emptying, which could contribute to ritonavir-induced gastrointestinal dysfunction. When S. baicalensis extract was administered to ritonavir-treated rats the delayed gastric emptying was significantly attenuated (P<0.05). The results suggest that S. baicalensis and the constituent baicalein reduce the gastrointestinal dysfunction caused by ritonavir. It is concluded that S. baicalensis may potentially have a role to play in reducing drug-induced adverse effects.

Scutellaria baicalensis decreases ritonavir-induced nausea

BackgroundProtease inhibitors, particularly ritonavir, causes significant gastrointestinal disturbances such as nausea, even at low doses. This ritonavir-induced nausea could be related to its oxidative stress in the gut. Alleviation of drug-induced nausea is important in effectively increasing patients' compliance and improving their quality of life. Conventional anti-emetic drugs can only partially abate the symptoms in these patients, and their cost has also been a concern. Rats respond to nausea-producing emetic stimuli by increasing consumption of non-nutritive substances like kaolin or clay, a phenomenon known as pica. In this study, we used this rat pica model to evaluate the effects of Scutellaria baicalensis, a commonly used oriental herbal medicine, on ritonavir-induced nausea.ResultsRats treated with 20 mg/kg ritonavir significant caused increases of kaolin consumption at 24 to 48 hr (P < 0.01). Pretreatment with 0.3 and 3 mg/kg Scutellaria baicalensis extract significantly decreased ritonavir-induced kaolin intake in a dose-related manner (P < 0.01). Compared to vehicle treatment, the extract completely prevented ritonavir-induced kaolin consumption at dose 3 mg/kg. The area under the curves (AUC) for kaolin intake from time 0 to 120 hr for vehicle only, ritonavir only, SbE 0.3 mg/kg plus ritonavir, and SbE 3 mg/kg plus ritonavir were 27.3 g•hr, 146.7 g•hr, 123.2 g•hr, and 32.7 g•hr, respectively. The reduction in area under the curves of kaolin intake from time 0 to 120 hr between ritonavir only and SbE 0.3 mg/kg plus ritonavir, ritonavir only and SbE 3 mg/kg plus ritonavir were 16.0% and 77.7%, respectively.ConclusionScutellaria baicalensis significantly attenuated ritonavir-induced pica, and demonstrated a potential in treating ritonavir-induced nausea.

American ginseng berry extract and ginsenoside Re attenuate cisplatin-induced kaolin intake in rats

Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsible for these symptoms. We tested whether pretreatment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model. In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cisplatin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE (dose range 50-150 mg/kg, IP) or ginsenoside Re (2 and 5 mg/kg, IP). Rats were treated with cisplatin (3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectroscopy. A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved significantly at this dose (P<0.05). Pretreatment with ginsenoside Re (5 mg/kg) also decreased kaolin intake (P<0.05). In vitro studies demonstrated a concentration-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals. Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemotherapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the conclusion that AGBE may exert an antinausea/antiemetic effect.

Effects of Ganoderma lucidum Extract on Chemotherapy-Induced Nausea and Vomiting in a Rat Model

Chemotherapy is highly cytotoxic, causing a number of severe adverse effects such as nausea and vomiting. Herbal medicines, which can often be used on a daily basis for prolonged treatment, may be clinically beneficial. Ganoderma lucidum or Lingzhi mushroom has been recognized as a remedy in treating a number of medical conditions, including balancing immunity and decreasing drug-induced side effects. It has been shown that rats react to emetic stimuli, like the chemotherapy agent cisplatin, by increased consumption of kaolin, known as pica; and this rat model has been utilized to evaluate novel anti-emetic compounds. In this study, we evaluated the effects of a G. lucidum extract (SunRecome, the most commonly used Lingzhi mushroom extract in China) in attenuating cisplatin-induced nausea and vomiting in the rat pica model. We observed that intraperitoneal cisplatin injection caused a significant increase in kaolin intake at 24, 48, 72 and 96 hours, reflecting cisplatin's nausea and vomiting action. This cisplatin-induced kaolin intake dose-dependently decreased after 1, 3 and 10 mg/kg G. lucidum extract injection (p < 0.01). In addition, there was a significant reduction of food intake after cisplatin. The cisplatin-induced food intake reduction improved significantly after G. lucidum extract administrations in a dose-related manner (p < 0.01), suggesting a supportive effect of the extract on general body condition. Future controlled clinical trials are needed to evaluate the safety and effectiveness of this herbal medication.

Effects of Antioxidant Herbs on Chemotherapy-Induced Nausea and Vomiting in a Rat-Pica Model

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.