A Clinical Evaluation of Guduchi (Tinospora cordifolia) and Yashtimadhu (Glycyrrhiza glabra) as Chemopreventive Agent in Cancer Treatment

Introduction

As human being constantly struggles against the changing environmental conditions to maintain optimum health and vigor throughout their life and with the increase in life expectancy and erratic way of dietary and lifestyle habits, we are witnessing an ever-growing menace of various lifestyle disorder and cancer is one of them. Cancer has emerged as a major public health concern not only in India but all over the world. Risk of developing cancer before the age of 75 years is 9.81% in males and 9.42% in females,¹ and death from cancer cases in India is 784,821 in 2017.² According to the World Health Organization, cancer is a second leading cause of death worldwide and accounted for 7. 6 million deaths (around 13% of all deaths) in 2008.³ The modern observations indicate now that most cancers are not of hereditary origin but environmental and lifestyle factors, such as dietary habits, smoking, alcohol consumption, infections, and pollution have a profound influence on the development of cancer.⁴ The contribution of genetic factors and environmental factors toward cancer risk is 5 to 10% and 90 to 95%, respectively, according to a research.⁵

Modern medicine is used to treat cancer with chemotherapy, radiotherapy, surgery, etc. In the last few years, after vigorous researches regarding safety, the efficacy profiles of radiotherapy and chemotherapy have been improved significantly. However, these therapies still produce severe undesired adverse effects such as anorexia–cachexia syndrome, fatigue, alopecia, loss of appetite and weight, diarrhea, nausea, vomiting, and mucositis, and other metabolic, hormonal disturbances. These adverse effects force the patients to discontinue the treatment and make their life miserable and pitiful. In a report, cancer patients (∼20%) treated annually with chemotherapy and radiotherapy are cured and an additional 20% may experience significant prolongation of life, while the remaining 60% have minimal or no benefit from these modes of treatment and suffer from its early and delayed toxic adverse effects.⁶

In Ayurveda, considering the various symptoms, cancerous type of growths and pathogenesis of cancer can be correlated and described under various types of arbuda (tumor), granthi (nodule) and asadhya (incurable), or sannipataj (when all the tridosha—vata, pitta, kapha—are involved) condition of various diseases. According to Acharya Sushurta when the doshas vitiate any part of the body and afflict the mamsa (muscle), med (fatty tissue) and twaka (skin), swelling is produced, which is vrittam (circular), sthiram (fixed), mand ruja (slightly painful), mahantama (big in size), analpmulam (broad based in situ), chiravruddhi (slowly growing), and achaya (does not suppurate) is called arbuda.⁷ Various types of herbs, various procedure of surgery, agnikarma, kshar-karma, and lifestyle modification are to be mentioned and conducted for the treatment of arbuda⁸ in Ayurveda, since samhita kala (1500–500 BC). The properties of chemotherapy drugs are very much similar with the 10 guna (properties) of visha (toxin) and agni pradhan dravya (herbs with quick and acute action) as mentioned in Ayurveda texts.⁹ So both can be correlated strongly.

Owing to the rise in awareness about the cancer, its treatments, and undesirable possible adverse effects of chemotherapy, more and more people are opting for a safe and cost-effective treatment options. In the past few years, there is a growing interest in Ayurveda and herbal sectors worldwide. In the present era, practicing ayurvedic system along with allopathic system of medicine can act as complementary to each other and following the concept of integrative oncology Ayurveda can help in improving and augmenting the quality of life of cancer patients treated with chemotherapy. Guduchi and yashtimadhu both drugs were used for integrated clinically study because of its balya and rasayana^10,11,12 (rejuvenative), pandu kamla har^10,13 (improve anemia and jaundice) ayushprada¹¹ (promotes life), vayah-sthapana^10,11,13 (antiaging), raktpittaghana¹⁴ and vishaghan¹⁰ (blood and body detoxification) and varnropana and shothhar^12,15 (wound healing, anti-inflammation), medhya^16,17 (brain tonic) and keshya^10,15 (improve hair health) properties. Modern study has also revealed some useful pharmacological effects of guduchi such as it is anti-inflammatory,¹⁸ it improves learning and memory,¹⁹ it acts as radioprotector and cyto-protector,^20,21 it increases life span (a study by Jamnagar-based Gujarat Ayurved University was conducted on the consumption of Guduchi [heart-leaved moonseed] that increased the lifespan of the common fruit fly [Drosophila melanogaster]), it is an antioxidant and has gastro-protective effects.²² Yashtimadhu has healing, antiulcer and regenerative properties,²³ immunostimulatory,²⁴ antiinfective, antiviral,²⁵ antioxidant,²⁶ antianxiolytic activity,²⁷ etc. All above properties of guduchi and yashtimadhu were very useful for this study.

Materials and Methods

Observations

It was observed that out of total patients in the present study, maximum patients (35.71, 24.99, and 17.85%) were found in the age group of 51 to 60, 41 to 50, and 61 to 70 years, respectively. The predominance of cancer was 58.91% in males than in female patients (41.05%). Majority of the patients were from urban area (i.e., 66.07%) in compared to the rural area (i.e., 33.92%). About 21.42% patients reported to have a positive family history of cancer, while the remaining 78.57% reported negative family history. About 69.65% patients were reported addiction with alcohol, smoking, and Tobacco chewing, while 30.35% of patients were nonaddicted. Maximum 25.09% patients were suffering from head and neck cancer followed by liver cancer in 19.64% than breast cancer in 16.07%; 14.28% of patients were suffering from bladder/prostrate and cervix/uterus. Symptoms such as nausea and vomiting (chhardi/vamana) were observed in 76.78% of patients, mucositis in 62.5%, fatigue (daihik duarblya) in 82.14% of patients, and alopecia (khalitya) in 28.57% patients. Xerostomia (dryness in mouth) was present in 62.5% of the patients followed by excessive salivation in 35.71%, skin reaction in 30.35%, and tastelessness was found in 33.92% patients. Most of the patients (66.84%) were suffering from irregular bowel habit, that is, either diarrhea or constipation, indigestion, and acidity problems. In objective findings, most of the patients, that is, 55.35%, were between 7 and 10 gm% of hemoglobin level, 35.71% of patients had TLC below 5000/cu.mm, and 41.07% of patients had platelet counts between 1 and 1.5 lack/cu.mm. Blood urea and serum creatinine level were found normal in most of the patients; only 22% of patients were with increased level of blood urea and 32.14% of patients were with serum creatinine level above 1.5 mg/dL.

Results

The outcome showed that out of seven subjective assessment symptoms, group D showed maximum relief, that is, 96.78% in fatigue with p-value ≤ 0.001 that was highly significant, while 78.8% relief in group B (CT+G) with p-value was ≤0.01, and in group C this was 76.4% with p-value ≤0.01 in fatigue symptoms. Rest of the symptoms, that is, nausea and vomiting, mucositis, xerostomia, skin reaction, tastelessness, also showed significant to highly significant results, that is, 78 to 89% with p-value ≤0.05 to ≤ 0.01 (Table 1). It was alopecia that showed moderate effect in 58.8% of patients in group D, while it was mild significance as 35.7 and 46.5% in group B and group C. In control group A (CT+C) where no drug was given, 75% patients get worsen their all symptoms with p-value > 0.05 that was insignificant and rest of patients in this group remain unchanged or mildly improve. In objective assessment, most of the patients, that is, up to 78% in group D get improved their pathological parameters, while adjuvant therapy with guduchi and yashtimadhu was up to 68 and 64%, respectively. Hb, TLC, and platelet levels are significantly improved than blood urea and creatinine levels (Table 2).

In control group, 75% patients showed worsened results in all symptoms (Fig. 1). Adjuvant therapy with guduchi showed 60% Fig. 2), while adjuvant therapy with yashtimadhu showed 64% overall effectiveness (Fig. 3). Integrated adjuvant therapy with guduchi and yashtimadhu showed highest improvements, that is, 77% patients got relieved. Rest patients showed mild-to- moderate significance in adjuvant therapy groups as shown in Fig. 4. Study showed highly significance results on objective parameters especially in group D as compared with group B and C. Group A showed insignificance results.

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Fig. 1 Overall observation in control group A.

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Fig. 2 Overall observation in group B, adjuvant with guduchi (Tinospora cordifolia).

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Fig. 3 Overall observation in group C, adjuvant with yashtimadhu (Glycyrrhiza glabra).

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Fig. 4 Overall observation in group D, adjuvant with guduchi (Tinospora cordifolia) and yastimadhu (Glycyrrhiza glabra).

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Discussion

The overall outcome in both subjective and objective parameters, significance to highly significance difference, was found between before therapy and after therapy, with integrated adjuvant therapy of guduchi and yashtimadhu, especially in group D as compared with group B, C, and group A. There was marked improvement in fatigue (daihik dourbalta) symptom up to 96.78%; this may be because of madhur rasa (sweet), guru and snigdha guna and madhur vipaka of yashtimadhu that increased the rasadhatu (lymphatic tissues) in body and immunomodulator and antioxidant property of guduchi that eventually improve tissue strength and immunity. This also justifies the balya (increased body strength), rasayana (rejuvenative) and ayushprada (antiaging) properties of guduchi as mentioned in kaiyadeva nighantu¹³ and raj nighantus.¹⁶ The nausea and vomiting (chhardi/vaman) were significantly improved may be because of laghu guna, madhur vipaka, and chhardihara karma of guduchi (K.N. Aus.Vrg.1/7–10) and madhur rasa, madhur vipaka, amal-pittahar (antihyperacidity) karma of yashtimadhu that relieve nausea and vomiting in 89.42% of the patients. With agnideepana, pachana, and sangrahi karma of guduchi are because of laghu, tikta, and katu guna, all of these act as paachana, deepen, and laghav karma in the body and improve symptoms such as indigestion, loss of appetite, flatulence, diarrhea, and bowel movements, which prove that these guna improve the functioning of liver enzymes and other digestive juices also, which enhance the patient’s nutritious requirement and strength as well, but all of these symptoms were worse in control group. Similarly,xerostomia (dryness in mouth), skin reaction (vivarnta, udarda), and tastelessness (partial loss of taste) produced by chemotherapy drugs, these symptoms were more relieved in adjuvant with yashtimadhu and combined therapy group. This effect may be because of tridhoshhar, immunomodulator,²⁹ and dhatushodhak¹⁶ properties of guduchi and due to yashtimadhu which is a potent vat-pittashamaka (reduce vitiated Vat and Pitta in body), snehana (emollient), kanthya (beneficial for mouth and throat), shitapittavinashini (cure urticaria and skin reactions), vrishya (aphrodisiac), soshanashaka (relives cachexia, dryness in body) as mentioned in dravyaguna hastamalaka¹² and in dhanwantari Nighantu.¹¹ These karma also increased “Oj” (vital energy) dhatu in body because of madhur rasa, madhur vipaka, and rasayana prabhava. And further all these properties managed vata and pitta prokopa-related symptoms such as xerostomia, urticaria, skin reactions, tastelessness, cancer cachexia, and fever, as results of this study also showed.

It was quite satisfaction to notice that except for 13 patients, the Hb gm%, TLC, platelet counts, and serum urea and creatinine levels of the 25 patients showed good improvement. This fact again favors the already established pandukamlahar¹³ (improved Hb level and jaundice) raktshodhak¹⁴ (blood purifying and detoxifying) and vishghan (antitoxicity) properties of guduchi and yashtimadhu that also improve platelet counts, blood urea, and serum. creatinine level in most of the patients. Low confidence, sleeplessness, body pain, and anxiety that were present in every patient got highly significant results with 78.64% of patients. This was also noticed that five patients showed mild to no significance response in spite of following the prescribed dietary and lifestyle measures along with the regular intake of guduchi or yashtimadhu or both for 90 days period. This may be because of chronicity, age factor, and patients suffering from the associated diseases. There were no adverse or undesirable side effects noted in terms of clinical presentation or laboratory investigation post studies. It is also important to note that Pathya-Apathya plays an important role in improving the symptoms as Acharya Charka also mentioned that “Pathya-Sevan produce healthy results and Apathya-Sevan induces Unhealthy results in body so it must be follows in every condition.”³⁰ The patients, who followed the prescribed diet and lifestyle guidelines diligently, responded well and took less time to recover. The present study illustrates that the overall integrated effect of guduchi and yashtimadhu, with its rasa (taste), guna (properties), veerya (potency), vipaka (digestion), and karma (action), corrects the metabolism, detoxifies the blood, and heals the inflammation, eventually helping in disintegrating the pathogenesis of adverse effects of chemotherapy.

Conclusion

This study illustrates the overall effect of guduchi (Tinospora cordifolia (Willd.) Miers ex Hook.f. and Thomas) and yashtimadhu (Glycyrrhiza glabra Linn.) with its properties, potency, and specific action (rasa guna, veerya, vipaka, karma, and prabhava) improving the general strength of body, correcting metabolism and neutralizing the toxic effects of blood and tissues and that is why it helps in reducing the adverse symptoms of chemotherapy and improves general strength of body as well. Vishahara (antitoxicity), varnropana (healing), raktaprasadana (improving blood quality), and rasayana (antiaging and immunomodulator) properties of both drugs helped to disintegrate the pathology of vata-pitta prokopa (vitiated vata and kaph dosha) and kapha kshaya (deficit of soft tissues), rasa-rakta dusti (impurities of lymph and blood) and oja (vital energy) and dhatu kshaya (deficit of tissues) produced by visha (toxic) and agni pradhandravyas (rapid acting drugs),that is, chemotherapy drugs within the body. So, with these results, we can say that it is feasible to practice ayurvedic and allopathic system of medicine that will act as complementary to each other. In this study, we conclude that guduchi and yashtimadhu both were very useful in improving and augmenting the quality of life of cancer patients treated with chemotherapy as an integrated approach.