INTRODUCTION:

The size of the global market for herbal medicines is estimated to be between US$80 and US$100 billion, and by the year 2010, this industry is projected to grow to US$2500 billion.^1,2 The demand for herbal treatments has increased significantly in recent years in the West. Since 1999, the market for herbal supplements has grown to more than US$15 billion worldwide, with US$7 billion in Europe, US$2.4 billion in Japan, US$2.7 billion in the rest of Asia, and US$3 billion in North America.³ According to the findings of a national survey, there was a significant rise in the number of people using alternative therapies between 1990 and 1997, with an estimated $27 billion in out-of-pocket costs.⁴

Natural resources abound in India, and traditional medicine and the utilisation of plants as a source of medication are both deeply ingrained and crucial elements of the country's healthcare system. 500 of the 1,500 therapeutic plants classified by the Indian system of medicine are utilised often.² In India, there are thought to be about 7800 manufacturing facilities for pharmaceuticals, and it is estimated that they use over 2,000 tonnes of herbs each year.⁵

Given the prevalence of herbal medicinal products (HMPs), it's critical to comprehend any possible interactions between herbs and prescription medications. Plant-drug interactions may be more likely than drug-drug interactions, if only because HMPs (even products made from a single herb) almost always contain combinations of pharmacologically active ingredients, as opposed to pharmaceuticals, which often contain single chemical entities. The objective of this systematic review is to evaluate the clinical data on pharmacological interactions involving HMPs.^6-7

Mechanisms of Drug Interactions with Herbal Medicines:

Most recorded pharmacological interactions with herbal remedies don't have fully understood underlying mechanisms. Similar to drug-drug interactions, these interactions involve pharmacokinetic and pharmacodynamic pathways (Figure 1).

Figure 1

Pharmacokinetic interactions are brought on by changes in the way that medications are absorbed, metabolised, distributed, or excreted. CYP activation and/or inhibition by herbal medications frequently leads to altered drug metabolism⁸.

The substrates of P- gp, fexofenadine and digoxin, which are frequently used as examinations for examining P- gp exertion in vivo, were set up to have increased concurrence in healthy subjects treated with St John’s wort⁹.

Herbal drugs are frequently administered orally and they can attain moderate to high attention in the gut lumen (the primary point of immersion for utmost orally- administered medicines) and liver, and may ply a significant effect on enterocytes and hepatocytes¹⁰

The lapping substrate particularity in the biotransformational pathways of the physiologic systems is seen as the major reason for medicine – medicine, food – medicine, and HDI (Marchetti et. al., 2007). The capability of different chemical halves to interact with receptor spots and alter physiological terrain can explain pharmacodynamic medicine relations while pharmacokinetic relations arise from altered immersion, hindrance in distribution pattern as well as changes and competition in the metabolic and excretory pathways¹¹

Medium of liver injury may include bioactivation of CYP, oxidative stress, mitochondrial injury, and apoptosis¹².

Drugs That Interact with Herbal Medicines in Humans:

Medicines that interact with herbal drugs substantially include anticoagulants (warfarin, aspirin and phenprocoumon), anodynes and antidepressants (midazolam, alprazolam, amitriptyline and trazodone), anti-HIV agents (indinavir and saquinavir), cardiovascular medicines (digoxin, nifedipine and propranolol), immunosuppressants (cyclosporine and tacrolimus) and anticancer medicines (irinotecan and imatinib). still, several other medicines, including ibuprofen, cilostazol, clopidogrel, acetaminophen, carbamazepine, mycophenolic acid, ritonavir and pravastatin are reported not to interact with herbal medicines¹³.

Theoretically, a medicine that's a binary substrate for CYP3A4 and P- gp has a much advanced eventuality for commerce with sauces that also modulate CYP3A4 and P- gp. For illustration, carbamazepine is metabolized by multiple CYPs but it is not a substrate of P- gp.¹⁴

Interaction of Herbs with Anti-biotics Drug:

Table: 1 Interactions of herbs with antibiotics

Sr. No	Antibiotic Drug	Herb	Interaction outcome
1.	Monomycin, kanamycin	Eleuthero	Effects of antibiotics
2.	Doxorubicin	Milk thistle, ubiquinone (coenzyme Q10)	¯Kidney toxicity herb may ¯cardiac side effects from these medications
3.	Adriamycin	Schizandra	¯ cardiotoxicity
4.	Penicillin V	Guar gum	Herb slows the absorption in the stomach
5.	Tacrolimus	St. John’s wort	¯ AUC by 57.8%
6.	Erythromycin	Digitalis	Erythromycin can the serum levels of digitalis glycosides increasing the therapeutic effects and risk of side effect

AUC: Area under the plasma concentration curve, ¯ : decrease; increase

Sauces with antidiabetic parcels An adding number of medicinal shops are being used to treat diabetes and its affiliated conditions. Te current NAPRALERT database lists over 1300 species of shops representing further than 750 rubrics within 190 families, covering lower shops similar as algae and fungi to nearly each types of advanced shops. numerous of these shops have been habituated ethno- pharmacologically in traditional drug as antidiabetics, particularly for T2DM^15-16

Interaction of herbs with Anti-ulcer Drug:

Ulcers are an open sore of the skin or mucus membrane characterized by sloughing of inflamed dead towel¹⁷.

Ulcers are lesions on the face of the skin or a mucous membrane characterized by a superficial loss of towel. Ulcers are most common on the skin of the lower extremities and in the gastrointestinal tract, although they may be encountered at nearly any point. Ulcers on the digestive tract membranes are called peptic ulcers (or stomach ulcers or duodenal ulcers)¹⁸.

The prevalence of duodenal ulcers has dropped significantly during the last many decades, while the prevalence of gastric ulcers has shown a small increase in recent times, which is substantially caused by the wide use of NSAIDs. The two most important developments associated with the overall dropped rats of peptic ulcer complaint are the discovery of effective and potent acid suppressants and the identification of. pylori as the main causative agent. In substance, as the contagious cause of gastric ulceration is being successfully fought, a advanced chance softheads. population is succumbing to gastritis and ulceration from the habitual consumption of drug, primarily NSAID¹⁹.

Mechanism of Action:

Studies in humans and beast models suggest that herbal drugs ply their salutary goods on gastric ulcer via multiple mechanisms, including antioxidant exertion, stimulation of mucosal proliferation, inhibition of acid product and stashing, increased mucus product, as well as inhibition of inflammation.

Fig. No. 2 Mechanism of action

SYMPTOMS:

· Burning stomach pain

· Feeling of fullness, bloating or belching

· Indole race to fatty foods

· Heartburn

· Nausea

Classification:

A. By region/area:

1. Duodenum (called duodenal ulcer)

2. Esophagus (called esophageal ulcer)

3. Stomach (called gastric ulcer)

4. Meckel’s diverticulum (called Meckel’s diverticulum ulcer; is very tender with palpation)

B. Modified Johnson classification of peptic ulcers:

· Type I:

Ulcer along the body of the stomach, most often along the lesser curve at incisura angularis along the locus minor is resistant. Not associated with acid hypersecretion.

· Type II:

Ulcer in the body in combination with duodenal ulcers. Associated with acid over secretion.

· Type III:

In the pyloric channel within 3 cm of pylorus. Associated with acid over secretion.

· Type IV:

Proximal gastroesophageal ulcer.

· Type V:

Can occur throughout the stomach associated with chronic use of NSAIDs (such as aspirin).[20]

Interaction of herbs with Anti-Hypertensive Drug:

Cardiovascular complaint (CVD) remains the leading cause of fragility and unseasonable death (WHO, 2013),²¹

Medium of Condiment- medicine Commerce A" possible commerce" refers to the possibility that one substance may alter the bioavailability, or the clinical effectiveness of another substance, when two or further substances are given coincidently. utmost of the possible relations may be classified in two major orders pharmacokinetic and pharma- codynamic interactions.²²

Cytochrome P- 450 (CYP) superfamily enzymes similar as CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 are responsible for oxidative metabolism of medicines (,12). CYP3A4 is a major contributor to the presystemic metabolism of medicines administered orally. Because CYP3A4 has an extremely wide substrate particularity and numerous in vitro and in vivo relations involving bioactive composites, it appears to intervene the oxidation of roughly 40- 50 of the medicines administered to humans²³.

Sr. No	Antihypertensive class	Drug	Interacting herb	Interaction outcomes	Reference
1.	Diuretic	Thiazides	Allium Sativum (Garlic	↑ Bioavailability and half-life of hydrochlorthiazide along with ↓ clearance and elimination rate	24
2.	Beta blockers	Propanolol	Piper nigrum (Black Piper)	↑ t max, Cmax, AUC by CYP 1A2 inhibition	25
3.	ACE inhibitor	Captopril	Allium Sativum (Garlic)	Produces synergistic antihypertensive effect	26
4.	Angiotensin-II receptor blocker	Losartan	Rhodiola rosea (Golden root)	↑ Cmax, AUC and CL	27
5.	Calcium channel blocker	Nifedipine	Hypericum perforatum (St Jhon’s wort)	↓ Cmax , AUC by Induction of CYP3A4	28

1 Diuretics:

Diuretics shows their effect on hypertension treatment by promoting the expatriation of urine( measured as the urine volume UV) excreted) and urinary sodium from the body and this helps reduce the volume of blood circulating through the cardiovascular system²⁹.

Thiazide and thiazide- suchlike diuretics are extensively used in the treatment of hypertension³⁰.

2 β-Blockers:

Enmity of adrenergic receptors affects the regulation of the rotation through several mechanisms, including a reduction in myocardial contractility, heart rate, and cardiac affair. leaguer of the beta receptors of the juxtaglomerular complex, reducing renin stashing and thereby dwindling product of circulating angiotensin II. This action likely contributes to the antihypertensive action of this class of medicines. Adrenergic receptor antagonists may lower blood pressure by other mechanisms, including revision of the control of the sympathetic nervous system at the position of the CNS, altered baroreceptor perceptivity, altered supplemental adrenergic neuron function, and increased prostacyclin biosynthesis³¹.

Interaction of herbs with Anti-Diabetics Agents:

Diabetes mellitus refers to a group of habitual metabolic conditions which are generally characterised by hyperglycaemia, which ultimately leads to damage of multiple body systems. Tere are two types of diabetes, type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. T1DM is appertained as insulin-dependent diabetes mellitus (IDDM) and is caused by the disabled product of insulin. T2DM, still, is generally associated with the incapability of cells to respond to insulin (insulin resistance) and hence appertained asnon-insulin dependent diabetes mellitus (NIDDM). Te frequence of diabetes has been adding encyclopedically. In 2015, an estimated 415 million grown-ups were living with diabetes, and this number is projected to increase to 642 million by 2040³².

Te global use of complementary and alternative medicine (CAM) for the management of diseases such as diabetes has rapidly increased over the last decade. It is reported that up to 72.8% of people with diabetes used herbal medicine, dietary supplements and other CAM therapies³³.

Exemplifications of common sauces and salutary supplements that have been used to treat diabetes include Momordica charantia, Trigonella foenum- graceum, Gymnema sylvestre, Azadirachta indica, l- carnitine, vanadium, chromium and vitamin E. Proposed mechanisms’ of action underpinning the antidiabetic goods of these composites include direct goods on insulin stashing, activation of glycogenesis and hepatic glycolysis, adrenomimeticism, pancreatic beta cell potassium channel blocker exertion, cAMP activation, and modulation of glucose immersion from the intestine^34–36.

Herb–drug interaction and its mechanisms of action:

Two (or further) medicines when administered together have the eventuality to beget chemical or pharmacological relations. similar relations may alter the effect of either agent, leading to dropped or increased effectiveness or inflexibility of adverse effects. Te issues are dependent on numerous chemical and pharmacological factors, similar as the physicochemical nature of the medicines in use and how they affect each other pharmacokinetically and pharmacodynamically (Fig. 1). Although, the mechanisms of relations between sauces and medicines are analogous, they are more complex in nature when several composites are involved. Herb – medicine relations (HDI) may afect clinical safety and efficacy via cumulative/ synergistic or negative relations among the herbal factors and medicine motes. Whilst negative or dangerous relations tend to admit further attention due to safety considerations, cumulative/ synergistic effects convinced by HDIs may result in an improvement of asked pharmacological efects. For illustration, the blood glucose lowering effect of antidiabetic medicines has been shown to be increased by agrimony³⁷.

Herb–antidiabetic drug co-administration studies:

Sr. No	*Herb*	Co-administered anti-diabetic drug	Experimental/ clinical study	Observation	References
1.	Aloe vera	Glibenclamide	Clinical	Additive effect on blood glucose lowering	39, 40
2.	Andrographis paniculata	NA	Experimental	Antihyperglycaemic effect Inhibits CYP2C19 activity	41,42
3.	Cassia	Glibenclamide	Experimental	Comparable effect to glibenclamide	43
4.	Ginseng (Ginsenoside CK)	Metformin	Experimental	Combined treatment with CK—ginsenoside and metformin has shown enhanced efect compared to individual compounds. Significant improvements were observed in plasma glucose and insulin levels	44
5.	Ginger (Zingiber offcinale)	Glibenclamide	Experimental	Combination with ginger extract reduces blood glucose level greater than glibenclamide alone	45

In Australia, diabetes is among the top 10 leading causes of death and was responsible for 3% of all Australian deaths in 2011, whereby the most common cause of diabetes related death was coronary heart disease, accounting for 64% of deaths from diabetes ⁴⁶

Several pharmaceutical agents efective in reducing diabetic mortalities (e.g., 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have also been shown to have antioxidant activities ⁴⁷.

Interaction of herbs with Anti-Cancer Drug:

According to the World Health Organization, cancer was one of the top 10 causes of worldwide death in 2019⁴⁸.

In 2020, there were,636 new cases of cases with cancer and,866 deaths from cancer reported in Thailand⁴⁹.

Cancer is a group of conditions caused by an abnormality in cell proliferation and isolation, which results in an irruption into organs, leading to metastasis and death⁵⁰.

All cancer survivors are at threat of cancer rush despite entering effective treatments, as some cancer cells remain in their bodies⁵¹. presently, cases with cancer are treated with numerous types of chemotherapeutic agents, which dispose them to high frequentness of adverse medicine responses and put them at high threat of medicine – medicine relations, performing insub-therapeutic goods or increased unwanted venom that could potentiate the negative issues of cancer remedy⁵².

Anticancer exertion:

Medicinal factory products flaunting anticancer exertion continue to be the subject of expansive exploration aimed at the development of medicines for the treatment of different mortal excrescences. The medicinal shops used for the treatment of cancer are, Acalypha fruticosa, Alangium lamarki, Catharanthus roseus, Celastrus paniculatus, Embelia ribes, Ficus glomerata, Ficus racemosa, Ocimum basilicum, Plumbago zeylanica, Terminalia chebula, Tylophora indica, Wrightia tinctoria. The excerpts used for the treatment of bone cancer is Buthus martensi, Colla cornu, Herba epimedii, Fructus lycii, Radix angelicae, Radix bupleuri, Rhizoma corydalis, Rhizoma curculiginis, Radix paeoniae, Radix glycyrrhizae, Scolopendra subspinipes, Squama manitis, Tuber curcumae. The herbal medicines used for treatment of pancreatic cancer are Emblica officinalis, Nigella sativa and Terminalia beleric^53,55.

REFERENCE:

1. Mathur A. Who owns traditional knowledge? Working Paper No. 96, Indian Council for Research on International Economic Relations; 2003. p. 1-33.

2. Agrawal OP, Raju PS. In: Abdin MZ, Abroi YP, editors. Global market of herbal products: Opportunities for India. Traditional system of medicine. Narosa Publishing House: New Delhi, India; 2006. p. 5-10.

3. Wakdikar S. Global health care challenge: Indian experiences and new prescriptions. Electronic J Biotechnol 2004; 7:214-20.

4. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: Results of a follow-up national survey. JAMA 1998; 28:1569-75.

5. Ramakrishnappa K. Biodiversity and the Ecosystem Approach in Agriculture, Forestry and Fisheries. New York, USA: 2003. Impact of Cultivation and Gathering of Medicinal Plants on Biodiversity: Case studies from India. United Nations Publications: p. 210-5.

6. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines. A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996. [Google Scholar]

7. Fetow CW, Avila JR. Complementary and Alternative Medicines. PA: Springhouse; 1999. [Google Scholar]

8. Moore, L.B. et al.St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc. Natl. Acad. Sci. U. S. A.2000; 97:7500–750.2

9. Durr, D. et al. St John’s wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin. Pharmacol. Ther.2000; 68:598–604.

10. Hennessy, M. et al. St John’s Wort increases expression of Pglycoprotein: implications for drug interactions. Br. J. Clin. Pharmacol. 2002; 53:75–82.

11. Rendic,S. Summary of information on mortal CYP enzymes mortal P450 metabolism data. medicine MetabRev. 2002; 34; 83 – 448. 4. Goodwin,B. et al. Regulation of the mortal CYP2B6 gene by the nuclear pregnane X receptor. Mol. Pharmacol. 2001; 60427 – 431.

12. Kaminsky,L.S. and Zhang,Z.Y.( 1997) mortal P450 metabolism of warfarin. Pharmacol. Ther.1997; 7367 – 74. 23. Lehmann,J.M. et al. The mortal orphan nuclear receptor PXR is actuated by composites that regulate CYP3A4 gene expression and cause medicine relations.J. Clin. Invest.1998; 1021016 – 1023.

13. Chang CL, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC. Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Altern Med eCAM. 2013; 2013:378657.

14. Mishra R, Mohd Shuaib S, Shiravan S, Mishra PS. A review on herbal antidiabetic drugs. J App Pharma Sci. 2011; 01:235–7.

15. Rhoades KR. Prescribed medications and OTCs: interactions and theming issues. Diabetes Spectrum. 2002; 15:256–261. Chan FK, Graham DY. Prevention of non-steroidal anti-inflammatory drug gastrointestinal complications reviews and recommendation based on risk assessment. Aliment Pharmacal There 2004; 19(10): 1051-1061.

16. Chan FK, Graham DY. Prevention of non-steroidal anti-inflammatory drug gastrointestinal complications reviews and recommendation based on risk assessment. Aliment Pharmacol Ther 2004; 19(10): 1051-1061.

17. Marshall BJ. "Helicobacter Pioneers: Firsthand accounts from the scientists who discovered helicobacter. Edn 3, Vol. I, Blackwell Science Asia Pty Ltd., Victoria, 2002, 1882–1992.

18. Marshall BJ. "Helicobacter Pioneers: Firsthand accounts from the scientists who discovered helicobacter. Edn 3, Vol. I, Blackwell Science Asia Pty Ltd., Victoria, 2002, 1882–1992 IAJPS 2022, 09 (5), 335 -344 Kavita Malviya Et al. IAJPS 2022, 09 (5), 335 -344 Kavita Malviya Et al.

19. Akinyemi A. J., Ademiluyi A. O., Oboh G. (2013). Aqueous extracts of two varieties of ginger (Zingiber officinale) inhibit angiotensin I-converting enzyme, iron(II), and sodium nitroprusside-induced lipid peroxidation in the rat heart in vitro. J. Med. Food 16, 641–646. 10.1089/jmf.2012.0022 [PubMed] [CrossRef] [Google Scholar]

20. Chen JK, Puente L. Interactions recognition and prevention of herb-drug, Medical Acupuncture A Journal For Physicians By Physicians, 1998 / 1999,10(2).

21. Budzinski JW, Foster BC, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures, Phytomedicine, 2000,7(4): 273-282

22. Asdaq SM, Inamdar MN. The potential for interaction of hydrochlorothiazide with garlic in rats, Chem. Biol. Interact, 2009,181: 472–479.

23. Bano G, Raina RK, Zutshi U et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers, Eur J Clin Pharmacol, 1991,41(6): 615-7.

24. Asdaq SMB, Inamdar MN, et al. Interaction of propranolol with garlic in Biochemical and Histological Changes in rat, Iranian Journal of Pharmaceutical Research, 2009,8(3): 201-20.

25. Spanakis M, Vizirianakis IS, et al. Pharmacokinetic Interaction between Losartan and Rhodiola rosea in Rabbits, Pharmacology, 2013 Jan 17,91(1-2): 112-116.

26. Wang XD, Li JL, et al. Rapid and simultaneous determination of nifedipine and dehydronifedipine in human plasma by liquid chromatography–tandem mass spectrometry: Application to a clinical herb–drug interaction study, J. Chromatogr. Biomed. Appl, 2007,852: 534–544.

27. Wright CI, Van-Buren L et al. Herbal medicines as diuretics: A review of the scientific evidence, Journal of Ethnopharmacology, 2007,114: 1–31.

28. Shah SU, Anjum S, et al. Use of diuretics in cardiovascular disease:(2) hypertension. Postgrad Med J, 2004,80: 271- 276.

29. Hardman JG, Limbird LE, Gilman, AG, The pharmacological basis of therapeutics, 11th edition, McGraw- Hill, New Delhi, 2006, 845.

30. Rahelic D. 7th edition of Idf diabetes Atlas-call for immediate action. Lijec Vjesn. 2016;138(1–2):57–8.

31. Chang HY, Wallis M, Tiralongo E. Use of complementary and alternative medicine among people living with diabetes: literature review. J Adv Nurs. 2007;58(4):307–19

32. Patel DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed. 2012;2(4):320–30.

33. Okoli CO, Obidike IC, Ezike AC, Akah PA, Salawu OA. Studies on the possible mechanisms of antidiabetic activity of extract of aerial parts of Phyllanthus niruri. Pharm Biol. 2011;49(3):248–55.

34. Hong SH, Heo JI, Kim JH, Kwon SO, Yeo KM, Bakowska-Barczak AM, Kolodziejczyk P, Ryu OH, Choi MK, Kang YH, et al. Antidiabetic and Beta cell-protection activities of purple corn anthocyanins. Biomol Ther (Seoul). 2013;21(4):284–9

35. Gray AM, Flatt PR. Actions of the traditional anti-diabetic plant, Agrimony eupatoria (agrimony): efects on hyperglycaemia, cellular glucose metabolism and insulin secretion. Br J Nutr. 1998;80(1):109–14

36. Yimam M, Zhao J, Corneliusen B, Pantier M, Brownell LA, Jia Q. UP780, a chromone-enriched aloe composition improves insulin sensitivity. Metab Syndr Relat Disord. 2013;11(4):267–75.

37. Bunyapraphatsara N, Yongchaiyudha S, Rungpitarangsi V, Chokechaijaroenporn O. Antidiabetic activity of Aloe vera L. juice II. Clinical trial in diabetes mellitus patients in combination with glibenclamide. Phytomed Int J Phytother Phytopharmacol. 1996;3(3):245–8.

38. Yu BC, Chen WC, Cheng JT. Antihyperclycaemic effect of andrographolide in streptozotocin-induced diabetic rats. Planta Med. 2003;69:1075–9.

39. Yu BC, Chen WC, Cheng JT. Antihyperclycaemic effect of andrographolide in streptozotocin-induced diabetic rats. Planta Med. 2003;69:1075–9.

40. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, Er HM, Ong CE. In vitro determination of the effect of Andrographis paniculata extracts and andrographolide on human hepatic cytochrome P450 activities. J Nat Med. 2011;65(3–4):440–7.

41. Cho WC, Chung WS, Lee SK, Leung AW, Cheng CH, Yue KK. Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efcacies in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2006;550(1–3):173–9.

42. Yoon SH, Han EJ, Sung JH, Chung SH. Anti-diabetic effects of compound K versus metformin versus compound K-metformin combination therapy in diabetic db/db mice. Biol Pharm Bull. 2007;30(11):2196–200.

43. Al-Omaria IL, Affb FU, Salhaba AS. Therapeutic effect and possible herb drug interactions of ginger (Zingiberofcinale Roscoe, Zingiberaceae) crude extract with glibenclamide and insulin. Pharmacognosy Comm. 2012;2:12–20.

44. Australian Institute of Health and Welfare. Cardiovascular disease, diabetes and chronic kidney disease-Australian facts: mortality. Cardiovascular, diabetes and chronic kidney disease, vol. 1. Canberra: AIHW; 2014.

45. Nasri H, Shirzad H, Baradaran A, Rafeian-Kopaei M. Antioxidant plants and diabetes mellitus. J Res Med Sci. 2015;20(5):491–502.

46. World Health Organization The Top 10 Causes of Death. [(accessed on 18 May 2021)]. Available online: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death

47. World Health Organization Thailand Fact Sheets. 2021. [(accessed on 18 May 2021)]. Available online: http://gco.iarc.fr/today/data/factsheets/populations/764-thailand-fact-sheets.pdf

48. World Health Organization Cancer. 2021. [(accessed on 18 May 2021)]. Available online: http://www.who.int/news-room/fact-sheets/detail/cancer

49. American Cancer Society Cancer Treatment and Survivorship Facts and Figures. 2019–2021. [(accessed on 18 May 2021)]. Available online: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-treatment-and-survivorship-facts-and-figures/cancer-treatment-and-survivorship-facts-and-figures-2019-2021.pdf

50. Balis F.M. Pharmacokinetic drug interactions of commonly used anticancer drugs. Clin. Pharm. 1986;11:223–235. doi: 10.2165/00003088-198611030-00004. [PubMed] [CrossRef] [Google Scholar].

51. Feng, Y; Wang, N; Zhu, M; Feng, Y; Li H and Tsao, S (2011), “Recent Progress on Anticancer Candidates in Patents of Herbal Medicinal Products; Recent Patents on Food”, Nutrition and Agriculture, 3 30-48

52. Rodeiro, I; Magarino, Y; Ocejo, O; Garrido, G and Delgado, R (2008), “Use of natural products in anti-cancer alternative therapy: risk of interactions with conventional anticancer drugs; Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 7 (6), 332-344.

53. Lalla, JK (2005), “Herbal medicines revisited”, The Pharma Review, 12, 101- 105.

Received on 24.02.2023 Modified on 10.04.2023

Research J. Science and Tech. 2023; 15(2):119-126.

DOI: 10.52711/2349-2988.2023.00020