Exploiting the nanotechnological approaches for traditional Chinese medicine in childhood rhinitis: A review of future perspectives

1 Introduction

Rhinitis is defined as the inflammation of the inner mucous lining of the nose with two or more symptoms (e.g., sneezing, nose itching, anterior or posterior rhinorrhea, and nasal obstruction) manifestations. It is further classified into three widely accepted groups: allergic rhinitis (AR), infectious rhinitis, and non-AR. However, this is an over-simplification of the types of rhinitis because a mixed phenotype exists in many patients [1]. The most common is AR, a symptom induced by various allergens that trigger an immunoglobulin E (IgE)-mediated response [2].

AR usually occurs in early childhood, with a prevalence of greater than 8.5 and 14% in children aged 6–7 and adolescents aged between 13 and 14 years, respectively [3]. Childhood rhinitis reduces the quality of life while affecting contiguous organs like sinuses, ears, and chest. It also causes problems with sleep, which further leads to reduced school performance and decreased participation in outdoor activities [4]. Evidence indicates that rhinitis is a common problem in childhood, which more than often remains undiagnosed. Due to late diagnosis and mismanagement, rhinitis negatively affects the quality of life of children [5].

The physical, social, and cognitive performance of children is affected due to the chronic symptoms of AR [6]. Effective treatment is essential to avoid the adverse effects of AR on children’s lifestyles and well-being. All types of treatments aim to manage the symptoms without changing the child’s capability to function; another essential aim is to avoid any complications or comorbidities caused by AR [7]. AR treatment comprises four significant parts: avoiding allergens, systematic nasal lavage, pharmacotherapy, and immunotherapy implementation. Currently, the most effective treatment is intranasal corticosteroids, accompanied by antihistamines, anti-leukotrienes, and sometimes immunotherapy [8]. Inflammation of the nasal mucosa is the hallmark of rhinitis, which poses a serious health risk, particularly in children. Even while traditional therapies like immunotherapy, intranasal corticosteroids, antihistamines, and anti-leukotrienes are frequently used, it is vital to take into account any possible side effects [9]. The mainstay of treatment, intranasal corticosteroids, can cause systemic side effects, including growth suppression in children as well as local ones like epistaxis and nose dryness [10]. Antihistamines can impair cognition and induce sleepiness, even though they are efficient in reducing symptoms. Anti-leukotrienes can also cause headaches and gastrointestinal problems [11]. Immunotherapy carries the danger of severe allergic reactions despite its potential benefits in certain circumstances. Traditional Chinese medicine (TCM), on the other hand, provides a more all-encompassing strategy with fewer side effects.

Individually targeted interventions such as immunotherapy are vital and can potentially avoid the further growth of allergen sensitization [12].

The Chinese philosophy of Yin Yang and its five elements is the foundation of TCM; it is situated on holistic ideologies and stresses harmony with the TCM universe. It is a complete medical system used to prevent, diagnose, and treat various diseases. TCM consists of multiple components, including acupuncture, herbal medicine, dietary therapy, moxibustion, and Chinese massage, known as “tui na” [13]. China is one of the few countries that has fully integrated traditional medicine into its healthcare system, and it has been practicing TCM and Western Medicine adjacent to each other since the nineteenth century. The most frequently used complementary and alternative medicine (CAM) therapy is herbal treatment derived from TCM [14]. Over the previous years, acceptance of CAM has increased in Western society as many herbs used in TCM have been integrated with Western Medicine. For instance, after Tu Youyou won the 2015 Nobel Prize in Physiology or Medicine for her discovery of a novel therapy against malaria, the herb Artemisia annua, also called sweet wormwood, became popular in Western society [15].

Panax ginseng is a widely used herb in modern medicine for relieving fatigue, improving focus, and enhancing immunity. Clinical trials provide evidence to support these indications; however, these properties have already been described in TCM [16]. Research shows that rhinitis is a common problem in childhood, affecting the quality of life, and treatment to relieve symptoms is highly necessary to avoid further complications and improve children’s physical and cognitive well-being [17]. TCM focuses on using holistic approaches, such as herbal medicine, diet therapy, and acupuncture, to prevent, relieve symptoms, or treat specific diseases. Therefore, there is a need to interrogate whether TCM can yield better results for treating childhood rhinitis when combined with nanotechnological advancements. This review aims to interrogate, explore, and identify the implications of nanotechnological approaches for TCM in childhood rhinitis.

All types of rhinorrhea – allergic, infectious, and non-allergic – present serious health risks to children, affecting not just their physical health but also their cognitive and social development [1,3,4]. In order to lessen the negative impacts of rhinitis on children’s quality of life, effective management techniques are essential [7]. In this regard, Yin Yang and the five elements serve as the foundation of TCM, which provides a comprehensive approach to disease prevention and treatment [13]. The incorporation of TCM into healthcare systems, especially in China, highlights its applicability in modern medicine [14]. Notably, a rising understanding of the potential efficacy of CAM therapies is reflected in the increased adoption of these treatments, including herbal remedies derived from TCM [15].

It is important to explain TCM applicability and possible benefits to pediatric treatment when discussing it in relation to childhood rhinitis. The general application of nano-based TCMs is illustrated in Figure 1. TCM provides a comprehensive approach to treatment, highlighting the interdependence of bodily systems and the significance of harmony and balance for optimum health [13]. Examining alternative therapy options outside of traditional Western medicine is relevant since pediatric rhinitis is a persistent and complex condition [16,17].

Figure 1

Structural illustration of applications in nano-drugs of TCMs. Adapted from the study of Qiu et al. [21].

Exploring the possible synergies between TCM and contemporary scientific techniques, including nanotechnology, provides a promising route for enhancing therapy results, given the complex nature of childhood rhinitis and the holistic principles of TCM [16,17]. This study looks at how advances in nanotechnology can improve TCM-based treatments for children with rhinitis, aiming to close the gap between traditional healing modalities and mainstream pediatric care.

2 Methodology

A methodical approach was used in this review to choose pertinent literature about the application of TCM techniques to the treatment of childhood rhinitis. To guarantee the selection of relevant articles, inclusion criteria were developed. The inclusion was limited to articles that had been published in peer-reviewed journals. Second, articles explicitly addressing TCM interventions for treating pediatric rhinitis were incorporated. Third, English-language articles were chosen in order to improve accessibility and comprehension. Finally, only publications released in the previous 10 years (2000–2024) were considered for the review in order to guarantee the accuracy of the data.

3 Childhood rhinitis

Rhinitis is a common condition resulting from irritation or inflammation of the nasal mucosa. Although nasal blockage is the most common symptom, runny nose, frequent sneezing, or nasal itching may be more unpleasant in specific individuals. Viral infections and allergic reactions to airborne allergens are the most frequent causes of nasal irritation. A component of the common cold illness, viral rhinorrhoea may linger for up to 10 days. When general infection signs such as fever and malaise are missing, it might not be easy to distinguish between the several causes of short-lived rhinitis [18]. It is critical to differentiate between infectious, allergic, non-allergic, non-infectious, and chronic rhinosinusitis in cases of long-lasting rhinosinusitis. While nasal blockage, rhinorrhea, and sneezing may affect individuals with allergic and non-allergic AR, itchiness and ocular symptoms are more likely in cases of AR [19].

Rhinitis is categorized as either non-allergic or allergic. Among AR (usually seasonal or perennial, caused by allergy sensitivity coexists with ailments such as asthma and eczema), seasonal (“hay fever”) and permanent forms are distinguished (all year round). Adolescents and younger children are equally susceptible to AR. Underdiagnosed and undertreated AR occurs because parents may perceive it as a minor discomfort rather than a severe illness. Many patients or parents may not seek medical therapy for AR or may opt to use over-the-counter medications since the condition is not considered life-threatening [20]. However, AR degrades the quality of life; it impairs sleep and cognitive and psychomotor abilities, interferes with social interactions, and may even impede learning. Eczema and asthma are two more pediatric atopic illnesses that are often linked to AR. According to one research, AR coexisted with asthma in 59% of children [18].

Chronic non-AR (includes subtypes without allergic inflammation, such as vasomotor rhinitis) without systemic allergic inflammation or endonasal infection symptoms (negative SPT, negative total blood IgE, and RAST tests) [22]. Patients with non-AR include a diverse population that may be divided into a minimum of six subgroups: senile rhinorrhea, drug-induced rhinorrhea, hormone-induced rhinorrhea, and rhinorrhea in the elderly. There are four types of rhinorrhea: atrophic, idiopathic, occupational, and gustatory [12]. About 7% or 22 million individuals in the United States suffer from non-AR, which is one-third as common as AR. At least two-thirds of people with non-AR have vasomotor rhinitis, making it the most prevalent subtype of the condition [19].

Childhood rhinitis has several causes. The most frequent culprits are dust mites, mold, cockroach feces, animal dander, and pollen from grass, trees, or weeds (Figure 2a). Similar symptoms to those of allergic rhinorrhea may be caused by any object that emits tobacco smoke or solid smells. However, rather than being allergies, these compounds are irritants. Analogously, AR may result from several risk factors. The significant risk factors are genetics and heredity factors, environmental exposures, inhaled allergens, food and nutrition, and the significance of microbial exposures [23].

Figure 2

Possible causes (a) and mechanism (b) of AR. Adapted from the study of Li et al. [25].

A set of symptoms containing two or more nasal irritations, sneezing, rhinorrhea, and nasal obstruction is referred to as rhinitis. IgE-mediated AR is often caused by allergen sensitization via inhalation (Figure 2b). Childhood-onset rhinorrhea is a powerful indicator of adult- and adolescent-onset asthma. When linked to allergic sensitization, rhinitis in preschool-aged children in the German “Multizentrische Allergiestudie” birth cohort was shown to be a risk factor for later wheezing. This also applies to symptoms of chronic rhinitis caused by home dust mite sensitivity [19].

A number of areas of daily living, including physical health, academic performance, and psychosocial well-being, are severely disrupted by AR. The results of the research offer strong proof of the harm that AR causes to children. First, research indicates that AR disturbs sleep cycles, which leads to weariness during the day and worse cognitive performance [24]. Additionally, chronic rhinorrhea and nasal congestion make it difficult for kids to participate in physical activities, which negatively affects their general physical health. Second, children with AR frequently have poor academic performance, as shown by higher rates of school absences because of the intensity of their symptoms or related side effects such as sinusitis or otitis media [19]. Moreover, the cognitive deficit resulting from sleep disturbances and ongoing symptoms could impair focus and memory, which could have an impact on academic performance.

Finally, AR has a noticeable effect on psychological health, especially in teenagers. Studies show that teenagers with AR have increased rates of somatization, anxiety, and depression [24]. These conditions can reduce resilience and mental stability in general. Further aggravating psychological difficulties is the social stigma attached to outward manifestations such as rhinorrhea and nasal congestion, which can cause social disgrace and feelings of humiliation.

4 TCM

TCM has been used in China’s medical field for several years. The goal of developing TCM is to maintain equilibrium between the Yin and Yang energies of the body to remain healthy. It can be used in chronic diseases like cardiac, cancer, osteoarthritis, and autoimmune disorders [1]. TCM combines herbs, diet therapy, massage, acupuncture, tai chi, and moxibustion. TCM professionals use both physiological and psychological approaches to approach health issues. TCM has also become a point of interest for modern drug research departments. In 2015, TCM was awarded the Nobel Prize in Physiology and Medicine for its artemisinin-based approach toward malaria [26].

Acupuncture is a healing technique used in TCM to cure health problems. This technique inserts a needle into the skin at specific points to promote health. Many studies have shown that acupuncture is very effective for treating health problems. Multiple studies are available regarding acupuncture and its contribution to relieving osteoarthritis, back pain, and neck pain [27,28]. It is concluded that acupuncture is a safe and effective treatment to get relief from chronic pain. Several studies revealed that acupuncture helps improve pregnancy rates in women undergoing in vitro fertilization, which is a massive success in fertility and reproductive health [29,30]. The practitioner must be licensed and trained to ensure the safety and effectiveness of the procedure [31].

The use of herbal medicine is increasing daily and is also in demand as a complementary therapeutics, especially in North America and Europe. Herbal medicine is the extract of plants (flowers, seeds, roots, bark, and leaves). It is based on the Yin and Yang and the Five Element theory concept, which supports the natural healing process. Much research has shown that Chinese herbal medicine has beneficial effects on health. For example, ginseng has immune-boosting properties, and ginger helps in digestion [30].

More than 11,000 herbs related to pharmacology are mentioned in TCM. In the branch of TCM, various effective herbal formulas are available and used for treating both acute and chronic diseases [32]. Certain ingredients or extracts are present in these portions that molecularly target the body sites to cure. It is necessary to develop such methods or techniques to evaluate these active constituents and the quality of these formulas. TCM databases have been developed recently to access relevant and validated data regarding herbs, procedures, and TCM. These databases include Health Information Technology, TCM Integrated Database (TCMID), TCM Gene Database and Informatics Tool (TCMGeneDIT), and Encyclopedia of TCM (ETCM) [32,33].

Many studies have shown that herbal medicine is very effective in the treatment of AR and related symptoms [34,35,36]. A systemic review and meta-analysis included clinical trial evidence for 16 eligible randomized controlled trials (RCTs) on herbal medicine for AR and concluded that P. hybridus could offer an effective treatment for AR [37]. Another study conducted on herbal medicine included 34 RCTs for cough treatment, where substantial evidence for A. paniculata and ivy/primrose/thyme-based preparations and moderate evidence for P. sidoides against cough were observed [38].

5 TCM approaches to childhood rhinitis

Sneezing, rhinorrhea, nasal congestion, and nasal itching are symptoms of an upper respiratory tract condition known as AR. According to studies, the prevalence of AR symptoms varies from 1.5 to 24.5%. The mean prevalence of childhood AR in China is 3.9–16.8%. Boys have a higher childhood prevalence of AR as a single entity than girls [39]. Most of the patients reported having AR symptoms before the age of 20, with 40% having symptoms before the age of six. Research has indicated a connection between childhood asthma and AR [7].

When children with rhinoconjunctivitis receive effective therapy, their chances of developing asthma are reduced. Effective symptomatic management, allergen avoidance, systematic immunotherapy, and patient education are all part of the treatment for AR. While nasal allergy symptoms can be well managed with medicine, there are side effects, including local epistaxis, nasal dryness, discomfort from intranasal drugs, and sleepiness from antihistamines [40,41].

On the other hand, corticosteroid usage may prevent growth. AR is a symptom of a particular inflammatory mechanism. TCM is widely used among China’s pediatric population. Research has indicated that Chinese Herbal Medicine works well for adults. Nevertheless, no meta-analysis or systematic review has been performed to evaluate the safety and effectiveness of Chinese herbal compounds in young patients with AR [19].

Herbal remedies for AR are widely used in China. The biological mechanisms underlying AR, including IgE regulation, eosinophil cell apoptosis, T, adhesion molecule regulation, mast cell production, and concentration of nuclear transcription factors and chemokines, can all be altered by some herbs, with an overall efficacy of 80–90%. Magnolia flower (Magnolia biondii Pamp.), xanthium fruit (Xanthium strumarium subsp. Sibiricum (Patrin ex Widder) Greuter), astragalus root (Astragalus membranaceous (Fisch.) Bge.), paniculate cynanchum (Cynanchum paniculatum (Bge.) Kitag.), and licorice root (Glycyrrhiza uralensis Fisch [19]. Combined with other Chinese herbs, these are usually the principal constituents of herbal remedies. These herbs are generally the main constituents in herbal prescriptions combined with other Chinese herbs [42].

Based on statistical analysis and literature reviews [43], Astragalus root is the most commonly used Chinese herb (75.7%) for treating AR. It is followed by xanthium fruit (70.4%) and magnolia flower (53.9%) [44,45,46]. Histamine-induced spasms of the ileum and trachea were lessened in guinea pigs treated with magnolia flower extract [47]. About 32.4% of mice with AR responded well to xanthium fruit treatment. By preventing the release of histamine and ovalbumin-specific (OVA-specific) IgE and lowering eosinophil infiltration, xanthium fruit reduced the symptoms of rhinitis. These herbs work by altering a number of biological processes that underlie AR. For instance, it has been demonstrated that magnolia flower extract reduces histamine-induced spasms in the ileum and trachea in guinea pigs, indicating that it may have antiallergic properties [47,48]. In a similar vein, xanthium fruit has been effective in lowering ovalbumin-specific IgE levels and histamine release, which helps to relieve rhinitis symptoms [19].

Moreover, the immunomodulatory qualities of astragalus root, one of the most widely used herbs for treating AR, have been linked to the control of inflammatory mediators and improvement of immunological function [49]. Another important ingredient in herbal medicines, licorice root, has anti-inflammatory properties and can help reduce the itching and congestion in the nose caused by AR [50].

The biological mechanisms, chemical elements, and target chemical compositions of TCM are all considered. The study methodically examined the molecular mechanism of Chinese herbs in treating AR at the molecular level [48].

Although various medical treatments for rhinitis have been approved, many patients still do not gain complete relief from their symptoms. For this reason, they use complementary medicine treatments, such as acupuncture. Clinical trials indicate that this treatment improves patients’ quality of life by reducing rhinitis symptoms. Due to this evidence, the American Academy of Otolaryngology now recommends acupuncture as an optimal and effective treatment of rhinitis [51]. Similarly, acupressure is a component of TCM that has shown significant results in treating rhinitis and is often used in Germany. A systematic review revealed that acupressure leads to better symptom alleviation than 1% ephedrine nasal drops plus thermal therapy [52].

Evidence indicates that diet and nutrition are essential in the development of allergic diseases. Dietary factors also influence disease progression and severity. It has been suggested that high energy, saturated fat, protein, and low fiber intake increase the risk of asthma and AR [53]. In comparison, consuming many vegetables, fruits, olive oil, and fish is recommended to reduce the risk of AR [54]. Moreover, research shows that consuming more fiber relieves AR symptoms [55].

6 Clinical studies on the use of TCM for AR

In 2023, a study was executed in China to identify the primary herbal prescription for treating AR in children, uncover the mechanism based on the network of constituents, and investigate the critical signaling pathways [47]. In DongZhiMen Hospital, the medical records of children with AR who received TCM treatment between August 2009 and January 2020 were evaluated by a descriptive-analytic approach based on herbal characteristics [16]. Network pharmacology was employed to create the ingredient-target-pathway network using internet databases, Genecards, the KEGG pathway, Cytoscape software, and association criteria to mine critical prescriptions [56].

The principle of making prescriptions was as follows: “Pungent and warm herbs were used more frequently while cold-natured herbs were paid equal attention as warm-natured herbs,” according to an examination of 1,092 clinical visits. ChanTui, BaiZhi, CangErzi, and FangFeng comprised the main prescriptions. These herbs addressed 141 signaling pathways and 130 underlying targets of AR, primarily affecting immunoregulation and signal transduction. Based on these clinical records, FangFeng, BaiZhi, CangErzi, and ChanTui comprise the core prescription. It primarily affects the immune system and signal transduction pathway targets [57].

To identify the elements associated with anxiety and depression and to conduct a preliminary investigation into the distribution of TCM constitution among patients suffering from AR, a study was conducted in Beijing and Shanghai. A specialized physician in Beijing and Shanghai sought out AR patients between July 2020 and June 2021. Out of the 630 hospitalized patients surveyed, 516 (81.9%) completed the questionnaires, comprising 54.3% males and 45.7% females. Three measures were implemented. Patient Health Questionnaire-9, Generalized Anxiety Disorder Questionnaire (GAD-7), and Constitution in Chinese Medicine Questionnaire. The classification data were assessed using the χ ² and Fisher’s exact test, and the associated factors of depression and anxiety were investigated using multivariate logistic regression. Data from 516 patients with AR showed Yang deficiency was the most common first constitution (22.1%), while inherited-special was the most common constitution (21.6%). Anxiety affected one-third of AR patients (33.5%) and depression nearly affected half (46.5%) [41].

The most prevalent constitution in patients with anxiety was inherited-special (27.7%), whereas the most common form in patients with depression was Yang deficiency (26.7%). Gender, income, duration of symptoms, balance, Qi-deficiency, Yang-deficiency, phlegm-dampness, Qi-stagnation, and inherited constitutions were associated with depression; likewise, gender, duration of symptoms, questions, and Qi-deficiency were associated with anxiety [58]. Our research indicated that inherited-special and Yang-deficiency constitution types were the most prevalent types of AR. Anxiety and depression had to have high prevalence values. Mental disorders were more common in those with Qi deficiency, phlegm-dampness, Qi stagnation, and inherited-special constitutions than in the other groups. Regulating these significant aspects to control AR patients’ clinical health may be advantageous. Additionally, the government should implement suitable mental health treatment programs to provide psychiatric assistance [59].

It is predicted that all three treatments will help patients with COPD by lowering the incidence and duration of acute exacerbations, increasing their ability to exercise, and enhancing their psychosocial functioning [60]. Additionally, patients with COPD may benefit most from combining conventional medicine and TCM treatments due to their higher efficacy and economic evaluation [61].

It was determined that symptoms, including diarrhea, headaches, stomach aches, and dizziness, were likely caused by TCM therapy. Consuming Chinese formulae like Mu Tong, which include aristolochic acid, has been linked to an elevated risk of CKD, ESRD, and urinary tract cancer, according to retrospective observational studies [15].

7 Mechanisms of action

The two main pillars of TCM are Chinese herbal medicine and acupuncture, which have been used for millennia to treat symptoms similar to AR and are still widely employed in China today. According to some researchers, some Chinese herbs used to treat anaphylaxis likely function as traditional antihistamines by preventing the release of histamine, which results in unfavorable clinical symptoms of the condition [62]. Additionally, certain combinations of complex Chinese herbs may have mediated anti-inflammatory, antibacterial, and immune effects [63]. Acupuncture influences the immune system by changing the patterns of lymphocyte subpopulations to include more CD3⁺ CD4⁺ T lymphocyte cells and by altering the secretion patterns of cytokines to have more IL-8 and less IL-6 and IL-10. It is also known that acupuncture can change the functioning of the autonomic nervous system and induce the release of specific hormones, including somatostatin, beta-endorphin, substance P, and adrenocorticotrophic hormone [30].

According to Liu, AR is one of the most prevalent and dangerous public health issues affecting children and adolescents. Concerns regarding the potential side effects of synthetic medicines were common among AR patients. As a result, people look for complementary and alternative therapies, including TCM. TCM focuses on the significance of a comprehensive and recovery not only on treating the illness. The public favors TCM because of its safety profile [64]. More TCM for AR investigations have been created in the last decade. These trials demonstrated the safety and effectiveness of TCM therapy, including acupuncture and herbal medicines, in treating allergy diseases [52].

There has been a discussion on TCM’s mechanism of action in treating AR. Numerous Chinese herbal formulations used in this therapy contain plants with antiallergic, anti-inflammatory, or immune-modulating properties. These functions include suppressing the production or activity of mast cell mediators (such as histamine), suppressing the formation of an inflammatory response by chemical agents, and suppressing the activity of lymphocytes and macrophages as well as serum (IgE) levels [65]. Resveratol is an active agent of several Chinese herbal medicines, including Sangpi Qingfei Decoction, Sangxing Decoction, Huatan Sanren Decoction, Qingjin Huatan Decoction, etc. widely used for lung diseases, inhibits inflammation, oxidative stress, fibrosis, aging, and cancer (Figure 3) [66].

Figure 3

Possible mechanisms of Resveratol (a main constituent of TCM) against AR. Adapted from the study of Wang et al. [70].

Several herbs in the Chinese herbal formulas used in the treatment have reportedly been shown to have antiallergic and anti-inflammatory properties. According to Yang et al., perennial AR is a prevalent medical condition in Taiwan [67]. The prevalence rates for boys and girls aged 13–18 years were 42.0 and 34.0%, respectively. The prevalence percentage for those between the ages of 13 and 14 was much higher in metropolitan areas, reaching 43.6%. Some Chinese herbal remedies have been used to treat AR for a long time. The traditional Chinese herb Xin-yi-san (XYS) has been used for centuries to treat AR by relieving rhinorrhea and nasal blockage when combined with other medicines. Yang et al. documented the positive effects of a mixed herbal formula comprising Xin-yi-san, Xiao-ging-long-tang, and Xiang-sha-liu-jun-zi-tang on AR [47]. They showed that when phytohemagglutinin-stimulated peripheral mononuclear cells were exposed to the hybrid procedure, they produced significantly more IL-10 but less IFN-γ and IL-5. Additionally, following treatment, there was a significant suppression of COX-2 mRNA expression in PMNs stimulated with LPS. These findings imply that the treatment with the mixed formula may alter neutrophil and lymphocyte function. Their research revealed that the mixed herbal formula treatment reduced inflammation of the nasal mucosa by restoring the stimulatory effects of allergic nasal fluid in patients with AR, who had elevated serum IgE levels. Researchers reasoned that XYS is necessary for the mixed formula; XYS should help AR patients with nasal symptoms [68].

Xanthium fruit (Cang Er Zi) and magnolia flower (Xin Yi Hua) are frequently included in herbal formulae used in TCM medicine to ease nasal congestion, lessen nasal discharge, and treat symptoms related to AR [69]. These herbs work well to reduce the symptoms of AR because they have anti-inflammatory and antiallergic qualities. Furthermore, Ying Xiang (LI20), Bi Tong (EX-HN8), and Hegu (LI4) are acupuncture sites that are strategically employed to treat AR patients’ nasal congestion, lessen sneezing, and improve their overall respiratory health.

Having been used for over 5,000 years, TCM is an extensive ancient medical system that applies a profound understanding of the natural laws and patterns of the human body. According to TCM, the human body is a miniature version of the larger Universal macrocosm. Therefore, to achieve harmony and perfect health, humans must abide by the laws of the universe. These fundamental theories are still used by TCM practitioners today to comprehend, identify, and manage health issues. Harmony is the ultimate goal in TCM. Hence, a person’s internal Qi will naturally adapt to changes in the seasonal flow of nature’s Qi [71].

TCM acknowledges that illness may ensue if it cannot shift smoothly to the energies of the upcoming season for whatever reason. TCM is frequently understood by Western CAM practitioners and their patients or clients through acupuncture. Still, acupuncture is merely one of the main therapeutic approaches of this all-encompassing medical system founded on the knowledge of Qi, or life force. Chinese psychology, Qigong, herbal therapy, acupuncture, and healing foods are this primary forms of treatment [72].

Although treating AR with TCM seems promising, there are a number of drawbacks and difficulties that need to be taken into account. Patients may have differing results from one TCM treatment to another due to variations in the standardization and quality of herbal formulations. Furthermore, careful planning and communication between medical professionals and patients is required when integrating TCM with mainstream medical therapies. For some people, access to TCM services and financial considerations may be obstacles to therapy. It is essential to recognize these constraints in order to present a fair assessment of the viability and effectiveness of TCM therapies for AR.

8 Pharmacokinetics (PK) and pharmacodynamics (PD) of TCMs

PK and PD characterization of TCMs is faced with significant difficulties due to their chemical complexity (with hundreds of components of different chemical nature in a single herbal formulation or formula, wide concentration ranges, distinct physiochemical properties, etc.), undefined targets (multi-target), and unclear mechanisms of actions. These challenges are compounded by the interactions with biological systems, such as varied absorption, distribution, metabolism, and excretion profiles, and the interactions among co-existing substances [73,74]. To understand the PK profiles of TCMs, it is necessary to use different methodologies compared to those used for Western medications. This involves dealing with the chemical complexity of TCMs and considering the TCMs and their compound formulas as a whole. By doing so, we may gain a comprehensive and mechanistic understanding of the therapeutic benefits of TCMs. The advancement of analytical tools, systems biology, biochemical pharmacology, and multivariate data processing approaches has recently facilitated the development of PK solutions to address these difficulties [75].

Nevertheless, most PK investigations on TCMs have utilized methodologies designed for Western medications. These studies primarily investigate the systemic exposures of drug-related components, which have been observed to be insufficient in explaining the comprehensive therapeutic effects of TCMs. The integral PK technique uses the area under the concentration–time curve, or activity-weighted approach, to analyze the PK–PD relationship by considering the combined PK profiles of numerous structurally similar analogs (prototypes/metabolites). Cellular PK–PD is a valuable addition to standard PK–PD when drug targets are located within the cells rather than on the surface of the cell membrane or in the extracellular space. Given the established clinical advantages of TCMs, a reverse pharmacology approach based on the reverse PK technique has been suggested to expedite target identification and the development of novel drugs [76]. Recently, it has been shown that gut bacteria play multiple roles in the effectiveness and toxicity of drugs. During traditional oral consumption, it is unavoidable for TCMs to interact with the gut microbiota before entering systemic circulation. These interactions play a role in modifying the components of TCMs, targeting the peripheral tissues, and influencing the way the host’s body processes drugs. As a result, they add to the overall advantages of TCMs [77].

9 Challenges and limitations of using TCM for rhinitis

TCM is currently the best-preserved and most influential conventional medical system with the most significant number of users worldwide. Indirubin is the active ingredient of Danggui Longhui Wan, a plant mixture used in TCM to treat chronic diseases. The cultural divergence between Eastern and Western medicinal philosophies presents a significant hurdle in the global acceptance of TCM. While TCM emphasizes a holistic approach, focusing on the body’s energy flow, balance, and personalized treatments, Western Medicine often prioritizes scientific evidence, standardized treatments, and reductionist approaches. This difference in perspectives creates challenges in integrating TCM into mainstream healthcare systems in Western societies [78].

Regulatory barriers also impede the widespread adoption of TCM. Concerns regarding the safe quality and efficacy of TCM therapies persist due to variations in formulations, lack of standardized protocols, and limited understanding of mechanisms of action. Regulatory bodies in different countries have varying criteria for approving TCM practices and products, leading to inconsistencies and barriers to global acceptance [18].

The establishment of TCM quality standards usually includes the selection of quality markers, development of analytical methods, validation of the method, analysis of sufficient batches of samples, and finally, setting the limit requirement. Variability in raw materials, manufacturing processes, and formulations of TCM products contributes to concerns regarding their quality, safety, and effectiveness. The lack of standardized manufacturing practices and quality control measures in TCM production further intensifies these issues [79].

To ensure consistency, efforts to establish standardized procedures and quality control protocols for TCM products involve pharmacognosy, analytical chemistry, and molecular biology as well as potency and purity. Techniques such as chromatography, mass spectrometry, and DNA barcoding aid in identifying and quantifying active compounds, verifying authenticity, and assessing potential contaminants [71]. The individualized and holistic approach of TCM poses challenges in conducting clinical trials that adhere to the stringent criteria of double-masked, placebo-controlled studies common in Western Medicine; TCM treatments often involve a combination of therapies tailored to individual needs. They made it challenging to create standardized protocols for clinical trials [80].

The complex nature of TCM interventions makes it difficult to isolate and evaluate specific effects. This complexity can contribute to more significant placebo effects and biases in clinical trials, affecting the interpretation of results [81]. Understanding the cultural and contextual influences on patient expectations and responses is crucial in designing rigorous tests to assess the efficacy of TCM interventions [48]. Addressing these challenges requires interdisciplinary collaboration and innovative approaches [82].

Integrating modern scientific methodologies with traditional knowledge can bridge the gap and facilitate mutual understanding and acceptance. Nanotechnology holds promise in advancing TCM by overcoming standardization and quality control challenges. Nanoparticles enable targeted drug delivery, increased bioavailability, and controlled release of TCM compounds [45].

Encapsulation of herbal constituents in nanoparticles enhances their stability and effectiveness, potentially addressing concerns about variability in formulations and ensuring consistent therapeutic outcomes. Research exploring nanoscale delivery systems for TCM is ongoing, with the aim of optimizing the efficacy, safety, and standardization of TCM products. Collaboration among nanotechnology experts, pharmacologists, and TCM practitioners could revolutionize how TCM therapies are delivered and integrated into modern healthcare systems [1].

To overcome the challenges and limitations of TCM, safer nanomaterials with better bioavailability, better solubility, and the least amount of toxicity should be used.

The formulation of TCM must include proper protocols for handling the material, formulation, and variations in its production [83]. Work with competent regulatory authorities to develop concrete guidelines on nanotechnology integration within the TCM system. To resolve legal problems, it will also contain a definition of safety and efficacy criteria particulars to these formulations that should be determined on the basis of evidence [84].

10 Nanotechnology for improving the therapeutic efficacy of TCM in AR

The field of nanotechnology involves the modification of materials and systems at the molecular level. The creation of drug delivery vehicles using nanoparticles has been made possible by its application to medicine or nanomedicine. These nanocarriers can carry and deliver medication to illness locations; they are typically less than 100 nm in size. It is an innovative technology that emerged in the 1980s and became the foundation for many other twenty-first-century technologies [85].

The three leading technologies of the twenty-first century are thought to be information technology, biotechnology, and nanotechnology. Since the concept of “nano-traditional Chinese medicine” was introduced in 1988, there has been a growing focus on the application of nanoparticle technology in TCM research. Nano-TCM uses nanotechnology to create TCM’s practical components, parts, original medication, and compound preparation; it results from TCM nanocrystallization rather than a new type of medicine [46,86].

The physical, chemical, and biological properties of TCM undergo significant changes and provide novel PD when generated at the nanoscale. When compared to native TCM, nano-TCM improves the medicine’s bioavailability, intensifies its intended impact, and reduces side effects (as shown in Figure 4). In recent years, several reports on TCM nano-preparations have combined the benefits of TCM components in tumor therapy with nano-targeted drug delivery methods [13,86].

Figure 4

Different types of nanotechnology-based carriers can be used for TCMs. Used with the permission of the Royal Society of Chemistry from the study of Wei et al. [86].

However, several studies have recently tried to include TCM compounds in nanoparticle-based delivery systems to avoid their limited in vivo efficacy and systemic toxicity. Comparing these formulations with the original drug, several showed an increase in vivo stability, better tissue targeting, and higher bioavailability [87,88]. Cancer patient studies have shown that TCM-combination treatment has a favorable prognosis, less adverse responses, long-lasting curative benefits, control of intracellular marker protein expression, and lessened pharmacological side effects [89].

A nasal spray using green nanotechnology has been produced and suggested as a substitute therapy for rhinosinusitis and rhinitis. The droplet size distribution’s limited spray angle and range offer excellent nebulization and potential local deposits in the nasal cavity. Human keratinocytes were used in in vitro experiments to validate the excellent biocompatibility of vesicles and their capacity to successfully prevent hydrogen peroxide-induced oxidative damage to cells [90,91].

The rapid advancement of nanotechnology in conjunction with TCM has expanded the scope of TCM’s applicability. Additionally, it broadens the area of study and advances TCM modernization. As anticipated, TCM will be carefully designed into a nano-drug delivery system using nanotechnology, enhancing its therapeutic efficacy for illness prevention and cure based on the advantages of the nanoscale. The formulations, pertinent preparation techniques, and properties of nano-TCM are presented here. Furthermore, a thorough explanation of the primary outstanding achievements of nano-TCM has been provided [42].

Although it has been used for hundreds of years, TCM has recently gained prominence. The active components and fractions from TCM exhibit intriguing biological activities; nevertheless, their clinical application is hindered by their poor solubility, poor stability, short biological half-life, ease of metabolism, and quick elimination. Pharmaceutical sciences thus place a great deal of emphasis on finding solutions to these issues to increase the therapeutic efficacy of TCM medications. Nanocarriers have garnered more interest recently because of their superior and effective delivery of active TCM components or fractions [48].

The term “nanotraditional Chinese medicine,” or “nano-TCM,” describes bioactive components, medicinal materials, or complex prescriptions manufactured using nanotechnology with a size of approximately 100 nm [108]. A by-product of TCM modernization, nano-TCM uses nanotechnology in TCM. The primary method for analyzing TCM materials and complex prescriptions is mechanical crushing technology; nanoparticulate medication delivery systems are the primary method for nanosizing bioactive substances or bioactive elements of TCM. Many benefits can be obtained via nano-TCM, including increased bioavailability, fewer side effects, prolonged release, targeted distribution, improved pharmacological effects, and improved mode of administration. Nonetheless, there are still many issues in nano TCM research that need to be addressed. This theory system of TCM, preparatory technology, safety, stability, etc., are the primary obstacles to nano-TCM [31].

Using nanotechnology can address some of the limitations of TCM; it also offers intriguing prospects for treating childhood rhinitis [109]. Case studies demonstrate how TCM interventions are more effective when they incorporate nanotechnology. For example, a recent study on pediatric rhinitis patients showed that medication delivery systems enabled by nanotechnology enhanced the targeted distribution of TCM herbal extracts to the nasal mucosa, improving treatment effects [91]. Researchers optimized therapeutic efficacy while minimizing potential negative effects by encasing TCM chemicals in biocompatible nanoparticles, such as liposomes or polymeric carriers, which allowed for regulated release and sustained retention of active ingredients [110,111]. Furthermore, the development of innovative formulations like nasal sprays and nasal patches – which improve patient compliance and convenience – is made easier by nanotechnology.

The field of nanobiotechnology involves the creation and use of tiny instruments to study biological sciences. It has developed into a frontier, becoming increasingly important in many vital areas, most notably healthcare in diagnostic and therapeutic applications. Nanobiotechnology holds great promise for advancing biological science and improving global healthcare services. Several novel nanoparticles and nanodevices that positively affect human health will probably be used soon [82] (Tables 1 and 2).

11 Conclusions

Children’s rhinitis induces significant challenges to their well-being and performance around the world. The results of this review discuss the potential of nanotechnological techniques in increasing the efficacy of TCM for childhood rhinitis. Childhood rhinitis, an inflammatory condition affecting the nasal mucosa, can have a harmful impact on the social, physical, and intellectual performance of children. Chronic symptoms require effective treatment to avoid long-term consequences on children’s well-being. TCM has traditionally been used for holistic rhinitis treatment but possesses limitations, such as poor water solubility, low bioavailability, single-use, and poor targeting ability, which have led to its decline in application. The integration of nanotechnology into TCM formulations eliminates these drawbacks by improving circulation time, bioavailability, and targeted distribution through the use of nanocarriers. The preparation of nanomaterials that are compatible with herbal extracts retains the therapeutic potential of active components that offer auspicious avenues for altering childhood rhinitis treatment techniques.

This review suggests more research initiatives in this multidisciplinary technique to harness the full potential of nanotechnological methods for childhood rhinitis treatment. By overcoming the limitations associated with traditional TCM administration, nanocarrier-based drug delivery systems have the potential to revolutionize the field, providing more effective and targeted treatment options. Future studies should focus on enhancing nanomaterial preparation, understanding their biocompatibility, and directing clinical trials to legalize regarding safety and efficacy in treating childhood rhinitis. This comprehensive roadmap can guide academics and healthcare specialists to in improving therapeutic strategies for handling childhood rhinitis using nanotechnological developments in TCM.

Future studies should put a high priority on closing these gaps and looking into fresh creative directions. To verify effectiveness and guarantee patient safety, standardizing nanotechnology-based TCM formulations, fine-tuning dosage schedules, and carrying out extensive clinical trials are essential. Furthermore, encouraging interdisciplinary cooperation among scientists, physicians, and business partners can hasten advancement and make it easier to convert research results into useful treatment plans.

By filling in these research gaps and looking forward to what lies ahead, the field can get closer to creating more individualized, efficient, and scientifically supported treatment plans for childhood rhinitis. In the end, these developments could greatly enhance the standard of living for pediatric patients and their families.