Effect,of,Chinese,herbal,medicine,on,lung,disease:an,updated,review

Virender Kumar,Davinder Kumar,Naveen Khatri*,Ashwani Kumar,Joginder Khurana

1College of Pharmacy,Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences,Rohatk 124001,Haryana,India.2Department of Pharmaceutical Sciences,Vishwavidyalaya,Jagjeetpur,Haridwar,Uttarakhand 249404,India.3Tirupati Wellness Ltd.,FH57+7Q7,Puruwala Santokhgarh,Himachal Pradesh 173021,India.

Abstract A large number of people worldwide suffer from pulmonary disorders,and their prevalence is on the rise.Although we have gained a greater understanding of the basis of respiratory airway disorders,the treatments and therapies available for those disorders have not progressed historically.Supplements to existing therapies are made from traditional natural derivatives and herbal medicines.Natural compounds such as these are capable of acting as the basis for developing new drugs and related treatments.Plants possess bioactive compounds that have distinct advantages over allopathic medicines because chemotherapy roots severe adverse effects rather than providing limited benefits.As a result of better effects and fewer adverse effects,herbal bioactive is a promising approach for treating respiratory disorders,resulting in a better quality of life and longer life expectancy for patients.Asthma,pulmonary fibrosis,lung cancer,and chronic obstructive pulmonary disease are among the pulmonary disorders addressed in the present article and approaches based on clinical trials.

Keywords:herbal drugs;delivery;lung cancer;asthma;respiratory disorders

Recent decades have seen a significant increase in interest in pulmonary drug delivery.Noninvasive drug administration can be achieved through the lungs,the main part of the respiratory system,because of their local and systemic effects[1].In comparison to other delivery methods,pulmonary delivery offers several advantages,including rapid uptake of drug,a large surface area for solute transport,improved absorption,and noninvasiveness[2–5].Pulmonary drug delivery is the process of depositing inhaled pharmacological agents in lower airways by inhaling drugs through the mouth.Diseases of the lungs are extremely dreadful.Several breathing problems can be attributed to lung diseases,such as asthma,pneumonia,chronic obstructive pulmonary disease,influenza,tuberculosis,lung cancer,and others[6].For topically acting or systemically acting drugs,pulmonary drug delivery targets the site of action in the lungs.A major advantage of pulmonary delivery is the possibility of using relatively low doses while reducing systemic side effects.A second advantage is some drugs’rapid onset of action and the possibility of producing fewer side effects[7,8].Supplements to existing therapies are made from traditional natural derivatives and herbal medicines.The development of new drugs can be based on these types of natural compounds.Hyperresponsive airways,eosinophilic inflammation,and mucus secretion are the main symptoms of asthma[9].The side effects of the drugs used for treating pulmonary disease are hypotension,shock,flushing,ankle edema,peptic ulcer,weight gain,etc.A trend has emerged toward using allopathic medicine,which is associated with fewer side effects due to the above-mentioned side effects.Herbal bioactive is hence conceptualized as a system of medicine that has no side effects,is safer,and has better efficacy than other medical systems.In this review,we will discuss about pulmonary delivery of herbal drugs with emphasis on the treatment of asthma,chronic obstructive pulmonary disease,lung cancer,and pulmonary fibrosis[10].

A literature survey was conducted to find essential papers on the effect of Chinese herbal medicine on lung disease using Chemical Abstract Service,PubMed and Web of Cancers.Search strategies were used to find out the relevant research articles using different keywords“Chinese”,“herbal”,“medicine”,“cancer”,“mechanism”,“lung disease”,“asthma”,“anti-tumor”,“cytotoxicity”and“respiratory disorders”.

Asthma

Over 5,000 years have passed since traditional medicine treated asthma[11].As an example of plant-based treatments,Chinese culture usesEphedra sinica,which provides immune system stimulation and reduces asthma crises[12].Plant-derived natural oils contain compounds such as phenylpropanoids and mono and sesquiterpenes,which are known for having anti-inflammatory and anesthetic properties and are used in the treatment of asthma[13].There is good evidence that honey,lemon,beets,yarrow,beets,onions,garlic,mint and other natural products,were effective treatment options for asthmatic children[14].Identifying candidate targets for combinatorial therapy for allergy pathogenesis is a major interest in Chinese medicine at present[15].In China,osteohole has a long history of use for asthma as part of the Chinese herbCnidii Fructus(Shechuangzi)[16].Role of herbal drugs in asthma is shown in Figure 1 and herbal drugs used traditionally for the treatment of asthma are shown in Table 1.

Figure 1 Role of herbal drugs in asthma

Chronic obstructive pulmonary disease(COPD)

Numerous herbal products are used in COPD.Several studies have shown thatGinseng Radixeffectively resolves COPD symptoms,including improved breathing ability.Peppermint herb contains menthol,having to sedate properties in respiratory muscles[40].A study has shown ginger improves lung circulation by breaking down mucus,reducing inflammation,and reducing mucus buildup.COPD can be minimized by taking vitamins as part of a healthy diet[41].It is common to observe vitamin D deficiencies in patients with COPD,which can easily be managed by consuming milk and products from it.When oxidants and antioxidants are not balanced,oxidative stress occurs.As a result,the lungs become inflamed,resulting in breathing difficulties.Antioxidant-rich foods,such as cranberries,apples,black beans,strawberries,ginger,olive oil,green tea,cherries and fish,can assist in reducing oxidative stress,thereby enhancing health[42].Tulsi shows immunomodulatory,antitussive,and expectorant properties,making it useful for asthma and COPD[43].

In addition to bettering the quality of life,improving lung function,reducing exacerbations,and increasing exercise capacity,traditional Chinese medicine has been used for centuries to treat COPD symptoms and signs.In a mouse model of COPD caused by cigarette smoke,Liujunzi Tang’s anti-inflammatory and anti-oxidative properties were demonstrated,inhibiting nuclear factor-κB activation and protectinglung function[44].Tulsi 50% aqueous ethanolic extract showed positive antiasthmatic effects in guinea pig models induced by histamine and acetylcholine.As a respiratory supplement,turmeric extract(Curcuma longa)is effective in treating COPD and asthma,running noses,allergies,and hyperactive bronchi.Sputum is reduced,coughing is relieved,and asthma is prevented by turmeric,which stops lipid peroxidation and scavenges free radicals[45].

Herbal bioactive has been shown to extend patient lives and improve quality of life.This is particularly useful in the treatment of lung cancer.Analgesic,antiangiogenic,antioxidant,anti-inflammatory,and antiseptic properties are attributed to curcumin,which is obtained from theCurcuma longaplant.Research shows that curcumin’s 0.6%concentration reduces cyclooxygenase 2 expression in subcutaneous tumors and increases survival rates in intrapulmonary tumors by decreasing cyclooxygenase 2 expression.See Figure 2.

Lung cancer patients mostly use herbs to reduce treatment side effects and symptoms,but they may also increase anticancer action directly.Traditional herbal medicines have a lot to offer,but they are also subject to adverse impacts or may reduce their effectiveness when compared to conventional treatments.Empirical evidence,case studies,and hypothetical physiological effects remain the primary justifications for using them[46].See Figure 3 and Table 2.

Table 2 Herbal drugs in lung cancer

Figure 2 Chinese herbal medicine for lung cancer

Figure 3 Role of herbal drugs in lung cancer

The extraction and identification of bioactive ingredients found inChinese herbal medicines have contributed significantly to treating lung diseases.Among these components is resveratrol,which is used to treat lung diseases.Cancer,aging,inflammation,fibrosis,and oxidative stress can be inhibited by resveratrol in vitro and in vivo[53,54].In ancient times,bufalin was obtained from toad venom as a traditional oriental cardiotonic steroid.Due to its cytotoxic properties,it was observed to reduce mitochondrial membrane potential and increase reactive oxygen species.Bufalin treatment increased proapoptotic protein levels while reducing antiapoptotic protein levels.Therefore,Bufalin’s antitumor activity caused apoptosis in lung cancer cells in vitro and reduced the size of tumors in vivo[54].Salvia miltiorrhiza Bungecontains cryptotanshinone,an active component.Cryptotanshinone treatment at a concentration of 20 mmol/L may induce apoptosis in A549 lung cancer cells in conjunction with upregulation of Bax,P53,and downregulation of Bcl-2.In vitro and in vivo,cryptotanshinone induces lung cancer cell apoptosis and may prevent tumorigenesis[55].Cinnamaldehyde,the primary organic compound of Cinnamomum cassia oil,is one of the most abundant organic compounds in the world.Various pathways may be used by cinnamonaldehyde to induce apoptosis in lung cancer cells in vitro and in vivo.Apoptosis is induced in lung cancer cells,and Epithelial-mesenchymal transition is reversed via the Wnt/β-catenin pathway[56].FromPuerariae Radix,puerarin can be isolated as an isoflavone.Various NSCLC cell lines were significantly inhibited by puerarin in vitro.Apoptosis via mitochondrial-mediated apoptosis was observed in NSCLC cells after puerarin treatment by flow cytometry[57].FZKA is a decoction that contains 12 different traditional herbs.Chinese doctors have used it for a long time to treat lung cancer patients in advanced stages.It is believed that FZKA promotes caspase-3,caspase-9,and PARP activities in lung cancer cells,thereby causing them to apoptose[58].Xiaoji decoction(XJD)inhibits lung cancer cell proliferation by inhibiting DNA methyltransferase 1 and transcription factor Sp via 5’AMP-activated protein kinase.According to XJD dose and time-dependent treatment,XJD induced A549 cell apoptosis by upregulating caspase-9 and BAD expressions via Akt signaling[59,60].

Pulmonary fibrosis(PF)

PF is characterized by scar tissue replacing the lung parenchyma in interstitial lung disease.The incidence of this disease is increasing worldwide,affecting millions of people[61].In addition to idiopathic PF,PF can occur due to autoimmune disease or exogenous exposure and is also seen in various clinical situations.This disease is often characterized by the death of epithelial cells followed by a leak of serum proteins and extravascular coagulation[62].PF is prevented through the use of the Jinshui Huanxian formula,which was developed according to Chinese medicinal theories and clinical practice.Clinical research demonstrated that Jinshui Huanxian formula alleviated clinical symptoms,slowed the progression of the disease,and improved the quality of life in people with PF.Anti-oxidant and antifibrotic effects have been demonstrated for many of these herbal drugs.The antioxidant activity of ginsenoside Rg1 is enhanced by increasing superoxide dismutase and catalase[63].Malondialdehyde levels are also reduced,and Nrf2 signaling is enhanced so that antifibrosis activity is induced.As a response to fibrosis,Rehmanniae Radixinhibits the process by downregulating parathyroid hormones,transforming growth factor 1,alpha-smooth muscle actin,and collagen-I expression[64].Through inhibition of Slug,Snail,and Twist expression and decrease of BLM-induced fibronectin,sulforaphane restores epithelial morphology in vitro[65].A BLM-induced mouse model of pulmonary fibrosis was mitigated by citrus alkaline extracts[66].Another study showed that methanolic extracts fromMyrtus communis(Myrtle)reduced inflammation,hydroxyproline levels,and lipid peroxidation.Catalase activity is also increased in PF mice by it[67].Inhalation of morin reduces the infiltration of inflammation cells and lowers the lung’s content of hydroxyproline,a flavonoid compound obtained fromMaclura pomifera[68].Various plant sources contain flavonoids,such as quercetin,which inhibits inflammatory cells from infiltrating the lungs,thereby reducing inflammation[69].See Figure 4.

Figure 4 Herbal Medicines in treatment of pulmonary fibrosis.

Clinical trial

Herbal therapy has been studied in a limited number of clinical trials for pulmonary disease.Several new clinical trials involving herbal treatment have been conducted in the past five years.Although most of them still emphasize whether a traditional formula or a modified formula is more effective than a traditional formula alone.Several herbs were used in Clark et al.’s study,including Mai-Men-Dong-Tang,Pycnogenol,Jia-Wei-Si-Jun-Zi-Tang,and Tylophora indica,to improve lung function[70].There are different studies related to using herbal or traditional drugs in reliving or treating asthma,as shown in Supplementary Table 1.

Conclusion

Studies have been conducted on medicinal plants that have antitumor properties.Plants continue to provide herbal medicines or biologically active compounds because many species are active in various experimental models.In order to standardize the extracts or characterize them chemically,further research is required.The results of this review,which suggests that many medicinal herbs can be administered through the lungs,provide insights into their potential for treating pulmonary diseases.Many studies have examined possible mechanisms of action,but most only present preliminary screening findings without describing the mechanism.There is evidence that patients suffering from lung diseases may benefit from using plant extracts,plant compounds,and traditional herbal medicines.In silico screening,high-throughput screening,model-based simulations,and systems modeling are all effective ways to identify new drugs for the pulmonary route that are safe and effective.New research suggests extracts may also be useful as adjuvants in the delivery of drugs to the lungs.Improving healthcare access and quality of life could contribute to better safety and benefits for people with pulmonary diseases.